Corneal inlay with nutrient transport structures

ABSTRACT

Corneal inlays and masks and methods of improving vision of a patient with corneal inlays and masks are provided. Masks with an aperture can improve the vision of a patient, such as by increasing the depth of focus of an eye of a patient. For example, a mask can have an annular portion with a relatively low visible light transmission surrounding a relatively high transmission central portion, such as a clear lens or aperture. This provides an annular mask with a small aperture for light to pass through to the retina to increase depth of focus. The mask may also include nutrient transport structures that provide nutrient flow through mask to prevent nutrient depletion. These nutrient transport structures can be configured to concentrate nutrient transmission near a center region of the mask to provide more nutrient flow near the center region.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/233,802, filed Aug. 13, 2009, the entirety of which is herebyincorporated by reference.

BACKGROUND

1. Field

This application relates generally to the field of corneal implants. Forexample, this application is directed to corneal inlays with an apertureto improve depth of focus (e.g. “masked” corneal inlays) and methods ofmaking.

2. Description of the Related Art

The human eye functions to provide vision by transmitting and focusinglight through a clear outer portion called the cornea, and furtherrefining the focus of the image by way of a crystalline lens onto aretina. The quality of the focused image depends on many factorsincluding the size and shape of the eye, and the transparency of thecornea and the lens.

The optical power of the eye is determined by the optical power of thecornea and the crystalline lens. In a normal, healthy eye, sharp imagesof distant objects are formed on the retina (emmetropia). In many eyes,images of distant objects are either formed in front of the retinabecause the eye is abnormally long or the cornea is abnormally steep(myopia), or formed in back of the retina because the eye is abnormallyshort or the cornea is abnormally flat (hyperopia). The cornea also maybe asymmetric or toric, resulting in an uncompensated cylindricalrefractive error referred to as corneal astigmatism.

A normally functioning human eye is capable of selectively focusing oneither near or far objects through a process known as accommodation.Accommodation is achieved by inducing deformation in a lens locatedinside the eye, which is referred to as the crystalline lens. Suchdeformation is induced by muscles called ciliary muscles. In mostindividuals, the ability to accommodate diminishes with age and theseindividuals cannot see up close without vision correction. If far visionalso is deficient, such individuals are usually prescribed bifocallenses.

SUMMARY

This application is directed to corneal inlays that are configured toposition an aperture or opening within optical path of an eye. Suchinlays can be useful for compensating for inadequate optical performanceof an eye, which may be the result of age. Presbyopia is one well-knownailment that involves the degradation of accommodation that can betreated with aperture corneal inlays. Inlays with an opening may also beuseful for treating aniridia.

An aperture corneal inlay can have many forms, such as including a lightblocking (e.g., opaque) annulus surrounding an aperture. Such a deviceis sometimes referred to herein as a “mask.” In some embodiments, thesmall aperture can be a pin-hole aperture. Long-term acceptance of suchinlays by patients can be enhanced by facilitating transmission ofnutrients between tissues located anteriorly and posteriorly of theinlay. For example, the inlay can be made porous such that certainnutrients can readily pass therethrough. If the inlay is very thin,small perforations or holes can be formed through the annulus for thispurpose.

In certain embodiments, a mask configured to be implanted in a cornea ofa patient to increase the depth of focus of the patient is provided. Themask can include an anterior surface configured to reside adjacent afirst corneal layer, a posterior surface configured to reside adjacent asecond corneal layer, and an aperture configured to transmit along anoptic axis light directed toward the aperture. The mask can furtherinclude a substantially opaque portion extending at least partiallybetween the aperture and an outer periphery of the mask, and the opaqueportion can include an inner region, an outer region, and a centralregion disposed between the inner and outer regions. A plurality ofholes can extend between the anterior surface and the posterior surface,and the holes can be positioned at locations in the inner, outer andcentral regions. The central region can include a first porosity, theinner region can include a second porosity, the outer region can includea third porosity, and the first porosity can be greater than the secondporosity or the third porosity.

In other embodiments, a mask can include an anterior surface configuredto reside adjacent a first corneal layer, a posterior surface configuredto reside adjacent a second corneal layer, and an aperture configured totransmit along an optic axis substantially all light directed toward theaperture. A substantially opaque portion can extend at least partiallybetween the aperture and an outer periphery of the mask, and the opaqueportion can include an inner region, an outer region, and a centralregion disposed between the inner and outer regions. The central regioncan include a first nutrient transport rate between the posterior andanterior surfaces, the inner region can include a second nutrienttransport rate between the posterior and anterior surfaces, the outerregion can include a third nutrient transport rate between the posteriorand anterior surfaces, and the first nutrient transport rate can begreater than the second or third nutrient transport rates.

In a further embodiment, a method for improving the vision of a patientis provided. The method can include providing a mask that includes ananterior surface configured to reside adjacent a first corneal layer, aposterior surface configured to reside adjacent a second corneal layer,and an aperture configured to transmit light along an optic axis. Themask can further include a substantially opaque portion extending atleast partially between the aperture and an outer periphery of the mask,and the opaque portion can include an inner region, an outer region, anda central region disposed between the inner and outer regions. Aplurality of holes can extend between the anterior surface and theposterior surface, and the holes can be positioned at locations in theinner, outer and central regions. The central region can include a firstporosity, the inner region can include a second porosity, the outerregion can include a third porosity, and the first porosity can begreater than the second porosity or the third porosity. The method canfurther include inserting the mask into a cornea.

In certain embodiments, a corneal inlay is provided. The corneal inlaycan include an anterior surface configured to reside adjacent a firstcorneal layer, a posterior surface configured to reside adjacent asecond corneal layer, and an opening configured to transmit lighttherethrough. The corneal inlay can further include an outer zoneadapted to substantially prevent transmission of light therethrough. Theouter zone can have nutrient transport structures disposed therein, andthe outer zone can be configured to provide enhanced nutrient flow atlocations spaced away from the outer periphery compared to locationsadjacent to the outer periphery.

The outer zone may comprise a first region and a second region at leastpartially disposed between the first region and the opening, and each ofthe first and second regions comprises nutrient transport structuresdisposed therein and one of the first and second regions is configuredto have enhanced nutrient transport compared to the other of the firstand second regions. The corneal inlay may also include a third regiondisposed between the region with enhanced nutrient transport and anouter or inner periphery of the corneal inlay. The region with enhancednutrient transport may be configured to have greater nutrient transportthan the third region. The corneal inlay can further include a firstannular band disposed adjacent the opening and a second annular banddisposed adjacent the outer periphery. The corneal inlay may alsoinclude one or more annular bands disposed adjacent the opening,adjacent an outer periphery of the corneal inlay, or both adjacent theopening and the outer periphery. The locations spaced away from theouter periphery can have higher porosity than locations adjacent to theouter periphery.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of the human eye.

FIG. 2 is a cross-sectional side view of the human eye.

FIG. 3 is a cross-sectional side view of the human eye of a presbyopicpatient wherein the light rays converge at a point behind the retina ofthe eye.

FIG. 4 is a cross-sectional side view of a presbyopic eye implanted withone embodiment of a mask wherein the light rays converge at a point onthe retina.

FIG. 5 is a plan view of the human eye with a mask applied thereto.

FIG. 6 is a perspective view of one embodiment of a mask.

FIG. 7 is a frontal plan view of an embodiment of a mask with ahexagon-shaped pinhole like aperture.

FIG. 8 is a frontal plan view of an embodiment of a mask with anoctagon-shaped pinhole like aperture.

FIG. 9 is a frontal plan view of an embodiment of a mask with anoval-shaped pinhole like aperture.

FIG. 10 is a frontal plan view of an embodiment of a mask with a pointedoval-shaped pinhole like aperture.

FIG. 11 is a frontal plan view of an embodiment of a mask with astar-shaped pinhole like aperture.

FIG. 12 is a frontal plan view of an embodiment of a mask with ateardrop-shaped pinhole like aperture spaced above the true center ofthe mask.

FIG. 13 is a frontal plan view of an embodiment of a mask with ateardrop-shaped pinhole like aperture centered within the mask.

FIG. 14 is a frontal plan view of an embodiment of a mask with ateardrop-shaped pinhole like aperture spaced below the true center ofthe mask.

FIG. 15 is a frontal plan view of an embodiment of a mask with asquare-shaped pinhole like aperture.

FIG. 16 is a frontal plan view of an embodiment of a mask with akidney-shaped oval pinhole like aperture.

FIG. 17 is a side view of an embodiment of a mask having varyingthickness.

FIG. 18 is a side view of another embodiment of a mask having varyingthickness.

FIG. 19 is a side view of an embodiment of a mask with a gel to provideopacity to the lens.

FIG. 20 is frontal plan view of an embodiment of a mask with a weave ofpolymeric fibers.

FIG. 21 is a side view of the mask of FIG. 20.

FIG. 22 is a frontal plan view of an embodiment of a mask having regionsof varying opacity.

FIG. 23 is a side view of the mask of FIG. 22.

FIG. 24 is a frontal plan view of an embodiment of a mask that includesa centrally located pinhole like aperture and radially extending slotsemanating from the center to the periphery of the mask.

FIG. 25 is a side view of the mask of FIG. 24.

FIG. 26 is a frontal plan view of an embodiment of a mask that includesa central pinhole like aperture, surrounded by a plurality of holesradially spaced from the pinhole like aperture and slots extendingradially spaced from the holes and extending to the periphery of themask.

FIG. 27 is a side view of the mask of FIG. 26.

FIG. 28 is a frontal plan view of an embodiment of a mask that includesa central pinhole like aperture, a region that includes a plurality ofholes radially spaced from the aperture, and a region that includesrectangular slots spaced radially from the holes.

FIG. 29 is a side view of the mask of FIG. 28.

FIG. 30 is a frontal plan view of an embodiment of a mask that includesa non-circular pinhole like aperture, a first set of slots radiallyspaced from the aperture, and a region that includes a second set ofslots extending to the periphery of the mask and radially spaced fromthe first set of slots.

FIG. 31 is a side view of the mask of FIG. 30.

FIG. 32 is a frontal plan view of an embodiment of a mask that includesa central pinhole like aperture and a plurality of holes radially spacedfrom the aperture.

FIG. 33 is a side view of the mask of FIG. 32.

FIG. 34 is an embodiment of a mask that includes two semi-circular maskportions.

FIG. 35 is an embodiment of a mask including two half-moon shapedportions.

FIG. 36 is an embodiment of a mask that includes a half-moon shapedregion and a centrally-located pinhole like aperture.

FIG. 37 is an enlarged, diagrammatic view of an embodiment of a maskthat includes particulate structure adapted for selectively controllinglight transmission through the mask in a low light environment.

FIG. 38 is a view of the mask of FIG. 37 in a bright light environment.

FIG. 39 is an embodiment of a mask that includes a barcode formed on theannular region of the mask.

FIG. 40 is another embodiment of a mask that includes connectors forsecuring the mask within the eye.

FIG. 41 is a plan view of an embodiment of a mask made of a spiraledfibrous strand.

FIG. 42 is a plan view of the mask of FIG. 41 being removed from theeye.

FIG. 43 is a top view of another embodiment of a mask configured toincrease depth of focus.

FIG. 43A is an enlarged view of a portion of the view of FIG. 43.

FIG. 44A is a cross-sectional view of the mask of FIG. 43A taken alongthe section plane 44-44.

FIG. 44B is a cross-sectional view similar to FIG. 44A of anotherembodiment of a mask.

FIG. 44C is a cross-sectional view similar to FIG. 44A of anotherembodiment of a mask.

FIG. 45A is a graphical representation of one arrangement of holes of aplurality of holes that may be formed on the mask of FIG. 43.

FIG. 45B is a graphical representation of another arrangement of holesof a plurality of holes that may be formed on the mask of FIG. 43.

FIG. 45C is a graphical representation of another arrangement of holesof a plurality of holes that may be formed on the mask of FIG. 43.

FIG. 46A is an enlarged view similar to that of FIG. 43A showing avariation of a mask having non-uniform size.

FIG. 46B is an enlarged view similar to that of FIG. 43A showing avariation of a mask having a non-uniform facet orientation.

FIG. 47 is a top view of another embodiment of a mask having a holeregion and a peripheral region.

FIG. 48 is a flow chart illustrating one method of aligning a mask withan axis of the eye based on observation of an anatomical feature of theeye.

FIG. 49 is a flow chart illustrating one method of screening a patientfor the use of a mask.

FIGS. 50A-50C show a mask, similar to those described herein, insertedbeneath an epithelium sheet of a cornea.

FIGS. 51A-51C show a mask, similar to those described herein, insertedbeneath a Bowman's membrane of a cornea.

FIG. 52 is a cross-sectional view of an eye illustrating a treatment ofa patient wherein a flap is opened to place an implant and a location ismarked for placement of the implant.

FIG. 52A is a partial plan view of the eye of FIG. 52 wherein an implanthas been applied to a corneal flap and positioned with respect to aring.

FIG. 53 is a cross-sectional view of an eye illustrating a treatment ofa patient wherein a pocket is created to place an implant and a locationis marked for placement of the implant.

FIG. 53A is a partial plan view of the eye of FIG. 53 wherein an implanthas been positioned in a pocket and positioned with respect to a ring.

FIG. 54 is a flow chart illustrating one method for making a mask from acomposition comprising a highly fluorinated polymer and an opacificationagent.

FIG. 55 is a front view of an embodiment of a mask with a plurality ofgenerally randomly distributed holes that have substantially equal sizeas described herein.

FIG. 56 is a front view of an embodiment of a mask with larger holesnear the center of the annulus as described herein.

FIG. 57 is a front view of an embodiment of a mask with a hole regionthat has three sub-regions as described herein.

FIG. 58 is a plot of radial distance from the center of the aperture asa function of percentage of epithelial glucose depletion for the masksof FIGS. 55 and 56.

DETAILED DESCRIPTION

This application is directed to corneal inlays (e.g., masks) forimproving the depth of focus of an eye of a patient and methods andapparatuses for making such corneal inlays. The masks generally employpin-hole vision correction and have nutrient transport structures insome embodiments. The masks may be applied to the eye in any manner andin any location, e.g., as an implant in the cornea (sometimes referredto as a “corneal inlay”). The masks can also be embodied in or combinedwith lenses and applied in other regions of the eye, e.g., as or incombination with contact lenses or intraocular lenses. In someapplications, discussed further below, the masks are formed of a stablematerial, e.g., one that can be implanted permanently. Corneal inlayswith an opening may also be used to treat aniridia.

I. Overview of Depth of Focus Vision Correction

As discussed above, mask that has a pinhole aperture may be used toimprove the depth of focus of a human eye. As discussed above,presbyopia is a problem of the human eye that commonly occurs in olderhuman adults wherein the ability to focus becomes limited to inadequaterange. FIGS. 1-6 illustrate how presbyopia interferes with the normalfunction of the eye and how a mask with a pinhole aperture mitigates theproblem.

FIG. 1 shows the human eye, and FIG. 2 is a side view of the eye 10. Theeye 10 includes a cornea 12 and an intraocular lens 14 posterior to thecornea 12. The cornea 12 is a first focusing element of the eye 10. Theintraocular lens 14 is a second focusing element of the eye 10. The eye10 also includes a retina 16, which lines the interior of the rearsurface of the eye 10. The retina 16 includes the receptor cells whichare primarily responsible for the sense of vision. The retina 16includes a highly sensitive region, known as the macula, where signalsare received and transmitted to the visual centers of the brain via theoptic nerve 18. The retina 16 also includes a point with particularlyhigh sensitivity 20, known as the fovea. As discussed in more detail inconnection with FIG. 8, the fovea 20 is slightly offset from the axis ofsymmetry of the eye 10.

The eye 10 also includes a ring of pigmented tissue known as the iris22. The iris 22 includes smooth muscle for controlling and regulatingthe size of an opening 24 in the iris 22, which is known as the pupil.An entrance pupil 26 is seen as the image of the iris 22 viewed throughthe cornea 12 (See FIG. 7). A central point of the entrance pupil 28 isillustrated in FIG. 7 and will be discussed further below.

The eye 10 resides in an eye-socket in the skull and is able to rotatetherein about a center of rotation 30.

FIG. 3 shows the transmission of light through the eye 10 of apresbyotic patient. Due to either an aberration in the cornea 12 or theintraocular lens 14, or loss of muscle control, light rays 32 enteringthe eye 10 and passing through the cornea 12 and the intraocular lens 14are refracted in such a way that the light rays 32 do not converge at asingle focal point on the retina 16. FIG. 3 illustrates that in apresbyotic patient, the light rays 32 often converge at a point behindthe retina 16. As a result, the patient experiences blurred vision.

Turning now to FIG. 4, there is shown the light transmission through theeye 10 to which a mask 34 has been applied. The mask 34 is shownimplanted in the cornea 12 in FIG. 4. However, as discussed below, itwill be understood that the mask 34 can be, in various modes ofapplication, implanted in the cornea 12 (as shown), used as a contactlens placed over the cornea 12, incorporated in the intraocular lens 14(including the patient's original lens or an implanted lens), orotherwise positioned on or in the eye 10. In the illustrated embodiment,the light rays 32 that pass through the mask 34, the cornea 12, and thelens 14 converge at a single focal point on the retina 16. The lightrays 32 that would not converge at the single point on retina 16 areblocked by the mask 34. As discussed below, it is desirable to positionthe mask 34 on the eye 10 so that the light rays 32 that pass throughthe mask 34 converge at the fovea 20.

Turning now to FIG. 6, there is shown one embodiment of the mask 34. Avariety of variations of the mask 34 are discussed hereinbelow. SectionIII discusses some materials that can be used to make the mask 34 andany of the variation thereof discussed hereinbelow. As seen, the mask 34preferably includes an annular region 36 surrounding a pinhole openingor aperture 38 substantially centrally located on the mask 34. Thepinhole aperture 38 is generally located around a central axis 39,referred to herein as the optical axis of the mask 34. The pinholeaperture 38 preferably is in the shape of a circle. It has been reportedthat a circular aperture, such as the aperture 38 may, in some patients,produce a so-called “halo effect” where the patient perceives ashimmering image around the object being viewed. Accordingly, it may bedesirable to provide an aperture 38 in a shape that diminishes, reduces,or completely eliminates the so-called “halo effect.”

II. Masks Employing Depth of Focus Correction

FIGS. 7-42 illustrate a variety of embodiments of masks that can improvethe vision of a patient with presbyopia. The masks described inconnection with FIG. 7-42 are similar to the mask 34, except asdescribed differently below. Any of the masks discussed below, e.g.,those shown in FIGS. 7-42, can be made of the materials discussed belowin Section III. The mask 34 and any of the masks discussed below caninclude a locator structure, such as is discussed in U.S. PatentPublication No. 2006/0235428, filed Apr. 14, 2005 with the title “OCULARINLAY WITH LOCATOR,” which is incorporated herein by reference in itsentirety. The masks described in connection with FIGS. 7-42 can be usedand applied to the eye 10 of a patient in a similar fashion to the mask34. For example, FIG. 7 shows an embodiment of a mask 34 a that includesan aperture 38 a formed in the shape of a hexagon. FIG. 8 shows anotherembodiment of a mask 34 b that includes an aperture 38 b formed in theshape of an octagon. FIG. 9 shows another embodiment of a mask 34 c thatincludes an aperture 38 c formed in the shape of an oval, while FIG. 10shows another embodiment of a mask 34 d that includes an aperture 38 dformed in the shape of a pointed oval. FIG. 11 shows another embodimentof a mask 34 e wherein the aperture 38 e is formed in the shape of astar or starburst.

FIGS. 12-14 illustrate further embodiments that have tear-drop shapedapertures. FIG. 12 shows a mask 34 f that has a tear-drop shapedaperture 38 f that is located above the true center of the mask 34 f.FIG. 13 shows a mask 34 g that has a tear-drop shaped aperture 38 g thatis substantially centered in the mask 34 g. FIG. 14 shows a mask 34 hthat has a tear-drop shaped aperture 38 h that is below the true centerof the mask 34 h. FIG. 12-14 illustrate that the position of aperturecan be tailored, e.g., centered or off-center, to provide differenteffects. For example, an aperture that is located below the true centerof a mask generally will allow more light to enter the eye because theupper portion of the aperture 34 will not be covered by the eyelid ofthe patient. Conversely, where the aperture is located above the truecenter of the mask, the aperture may be partially covered by the eyelid.Thus, the above-center aperture may permit less light to enter the eye.

FIG. 15 shows an embodiment of a mask 34 i that includes an aperture 38i formed in the shape of a square. FIG. 16 shows an embodiment of a mask34 j that has a kidney-shaped aperture 38 j. It will be appreciated thatthe apertures shown in FIGS. 7-16 are merely exemplary of non-circularapertures. Other shapes and arrangements may also be provided and arewithin the scope of the present invention.

The mask 34 preferably has a constant thickness, as discussed below.However, in some embodiments, the thickness of the mask may vary betweenthe inner periphery (near the aperture 38) and the outer periphery. FIG.17 shows a mask 34 k that has a convex profile, i.e., that has agradually decreasing thickness from the inner periphery to the outerperiphery. FIG. 18 shows a mask 34 l that has a concave profile, i.e.,that has a gradually increasing thickness from the inner periphery tothe outer periphery. Other cross-sectional profiles are also possible.

The annular region 36 is at least partially and preferably completelyopaque. The opacity of the annular region 36 prevents light from beingtransmitted through the mask 32 (as generally shown in FIG. 4). Opacityof the annular region 36 may be achieved in any of several differentways.

For example, in one embodiment, the material used to make mask 34 may benaturally opaque. Alternatively, the material used to make the mask 34may be substantially clear, but treated with a dye or other pigmentationagent to render region 36 substantially or completely opaque. In stillanother example, the surface of the mask 34 may be treated physically orchemically (such as by etching) to alter the refractive and transmissiveproperties of the mask 34 and make it less transmissive to light.

In still another alternative, the surface of the mask 34 may be treatedwith a particulate deposited thereon. For example, the surface of themask 34 may be deposited with particulate of titanium, gold or carbon toprovide opacity to the surface of the mask 34. In another alternative,the particulate may be encapsulated within the interior of the mask 34,as generally shown in FIG. 19. Finally, the mask 34 may be patterned toprovide areas of varying light transmissivity, as generally shown inFIGS. 24-33, which are discussed in detail below.

Turning to FIG. 20, there is shown a mask 34 m formed or made of a wovenfabric, such as a mesh of polyester fibers. The mesh may be across-hatched mesh of fibers. The mask 34 m includes an annular region36 m surrounding an aperture 38 m. The annular region 36 m comprises aplurality of generally regularly positioned apertures 36 m in the wovenfabric allow some light to pass through the mask 34 m. The amount oflight transmitted can be varied and controlled by, for example, movingthe fibers closer together or farther apart, as desired. Fibers moredensely distributed allow less light to pass through the annular region36 m. Alternatively, the thickness of fibers can be varied to allow moreor less light through the openings of the mesh. Making the fiber strandslarger results in the openings being smaller.

FIG. 22 shows an embodiment of a mask 34 n that includes an annularregion 36 n that has sub-regions with different opacities. The opacityof the annular region 36 n may gradually and progressively increase ordecrease, as desired. FIG. 22 shows one embodiment where a first area 42closest to an aperture 38 n has an opacity of approximately 43%. In thisembodiment, a second area 44, which is outlying with respect to thefirst area 42, has a greater opacity, such as 70%. In this embodiment, athird area 46, which is outlying with respect to the second area 42, hasan opacity of between 85 to 100%. The graduated opacity of the typedescribed above and shown in FIG. 22 is achieved in one embodiment by,for example, providing different degrees of pigmentation to the areas42, 44 and 46 of the mask 34 n. In another embodiment, light blockingmaterials of the type described above in variable degrees may beselectively deposited on the surface of a mask to achieve a graduatedopacity.

In another embodiment, the mask may be formed from co-extruded rods madeof material having different light transmissive properties. Theco-extruded rod may then be sliced to provide disks for a plurality ofmasks, such as those described herein.

FIGS. 24-33 shows examples of masks that have been modified to provideregions of differing opacity. For example, FIG. 24 shows a mask 34 othat includes an aperture 38 o and a plurality of cutouts 48 in thepattern of radial spokes extending from near the aperture 38 o to anouter periphery 50 of the mask 34 o. FIG. 24 shows that the cutouts 48are much more densely distributed about a circumference of the mask nearaperture 38 o than are the cutouts 48 about a circumference of the masknear the outer periphery 50. Accordingly, more light passes through themask 34 o nearer aperture 38 o than near the periphery 50. The change inlight transmission through the mask 34 o is gradual.

FIGS. 26-27 show another embodiment of a mask 34 p. The mask 34 pincludes an aperture 38 p and a plurality of circular cutouts 49 p, anda plurality of cutouts 51 p. The circular cutouts 49 p are locatedproximate the aperture 38 p. The cutouts 51 p are located between thecircular cutouts 49 p and the periphery 50 p. The density of thecircular cutouts 49 p generally decreases from the near the aperture 38p toward the periphery 50 p. The periphery 50 p of the mask 34 p isscalloped by the presence of the cutouts 51, which extend inward fromthe periphery 50 p, to allow some light to pass through the mask at theperiphery 50 p.

FIGS. 28-29 shows another embodiment similar to that of FIGS. 26-27wherein a mask 34 q includes a plurality of circular cutouts 49 q and aplurality of cutouts 51 q. The cutouts 51 q are disposed along theoutside periphery 50 q of the mask 34 q, but not so as to provide ascalloped periphery.

FIGS. 30 and 31 illustrate an embodiment of a mask 34 r that includes anannular region 36 r that is patterned and an aperture 38 r that isnon-circular. As shown in FIG. 30, the aperture 38 r is in the shape ofa starburst. Surrounding the aperture 38 r is a series of cutouts 51 rthat are more densely spaced toward the aperture 38 r. The mask 34 rincludes an outer periphery 50 r that is scalloped to provide additionallight transmission at the outer periphery 50 r.

FIGS. 32 and 33 show another embodiment of a mask 34 s that includes anannular region 36 s and an aperture 38 s. The annular region 36 s islocated between an outer periphery 50 s of the mask 34 s and theaperture 38 s. The annular region 36 s is patterned. In particular, aplurality of circular openings 56 s is distributed over the annularregion 36 s of the mask 34 s. It will be appreciated that the density ofthe openings 56 s is greater near the aperture 38 s than near theperiphery 50 s of the mask 34 s. As with the examples described above,this results in a gradual increase in the opacity of the mask 34 s fromaperture 38 s to periphery 50 s.

FIGS. 34-36 show further embodiments. In particular, FIG. 34 shows amask 34 t that includes a first mask portion 58 t and a second maskportion 60 t. The mask portions 58 t, 60 t are generally “C-shaped.” Asshown in FIG. 34, the mask portions 58 t, 60 t are implanted or insertedsuch that the mask portions 58 t, 60 t define a pinhole or aperture 38t.

FIG. 35 shows another embodiment wherein a mask 34 u includes two maskportions 58 u, 43 u. Each mask portion 58 u, 43 u is in the shape of ahalf-moon and is configured to be implanted or inserted in such a waythat the two halves define a central gap or opening 45 u, which permitslight to pass therethrough. Although opening 45 u is not a circularpinhole, the mask portions 58 u, 43 u in combination with the eyelid(shown as dashed line 47) of the patient provide a comparable pinholeeffect.

FIG. 36 shows another embodiment of a mask 34 v that includes anaperture 38 v and that is in the shape of a half-moon. As discussed inmore detail below, the mask 34 v may be implanted or inserted into alower portion of the cornea 12 where, as described above, thecombination of the mask 34 v and the eyelid 45 provides the pinholeeffect.

Other embodiments employ different ways of controlling the lighttransmissivity through a mask. For example, the mask may be a gel-filleddisk, as shown in FIG. 19. The gel may be a hydrogel or collagen, orother suitable material that is biocompatible with the mask material andcan be introduced into the interior of the mask. The gel within the maskmay include particulate 53 suspended within the gel. Examples ofsuitable particulate are gold, titanium, and carbon particulate, which,as discussed above, may alternatively be deposited on the surface of themask.

The material of the mask 34 may be any biocompatible polymeric material.Where a gel is used, the material is suitable for holding a gel.Examples of suitable materials for the mask 34 include the preferredpolymethylmethacrylate or other suitable polymers, such aspolycarbonates and the like. Of course, as indicated above, fornon-gel-filled materials, a preferred material may be a fibrousmaterial, such as a Dacron mesh.

The mask 34 may also be made to include a medicinal fluid or material,such as an antibiotic or other wound healing modulator that can beselectively released after application, insertion, or implantation ofthe mask 34 into the eye of the patient. Release of an antibiotic orother wound healing modulator after application, insertion, orimplantation provides faster and/or improved healing of the incision.The mask 34 may also be coated with other desired drugs or antibiotics.For example, it is known that cholesterol deposits can build up on theeye. Accordingly, the mask 34 may be provided with a releasablecholesterol deterring drug. The drug may be coated on the surface of themask 34 or, in an alternative embodiment, incorporated into thepolymeric material (such as PMMA) from which the mask 34 is formed.

FIGS. 37 and 38 illustrate one embodiment where a mask 34 w comprises aplurality of nanites 68. “Nanites” are small particulate structures thathave been adapted to selectively transmit or block light entering theeye of the patient. The particles may be of a very small size typical ofthe particles used in nanotechnology applications. The nanites 68 aresuspended in the gel or otherwise inserted into the interior of the mask34 w, as generally shown in FIGS. 37 and 38. The nanites 68 can bepreprogrammed to respond to different light environments.

Thus, as shown in FIG. 37, in a high light environment, the nanites 68turn and position themselves to substantially and selectively block someof the light from entering the eye. However, in a low light environmentwhere it is desirable for more light to enter the eye, nanites mayrespond by turning or be otherwise positioned to allow more light toenter the eye, as shown in FIG. 38.

Nano-devices or nanites are crystalline structures grown inlaboratories. The nanites may be treated such that they are receptive todifferent stimuli such as light. In accordance with one aspect of thepresent invention, the nanites can be imparted with energy where, inresponse to a low light and high light environments, they rotate in themanner described above and generally shown in FIG. 38.

Nanoscale devices and systems and their fabrication are described inSmith et al., “Nanofabrication,” Physics Today, February 1990, pp. 24-30and in Craighead, “Nanoelectromechanical Systems,” Science, Nov. 24,2000, Vol. 290, pp. 1502-1505, both of which are incorporated byreference herein in their entirety. Tailoring the properties ofsmall-sized particles for optical applications is disclosed in Chen etal. “Diffractive Phase Elements Based on Two-Dimensional ArtificialDielectrics,” Optics Letters, Jan. 15, 1995, Vol. 20, No. 2, pp.121-123, also incorporated by reference herein in its entirety.

Masks 34 made in accordance with the present invention may be furthermodified to include other properties. FIG. 39 shows one embodiment of amask 34 x that includes a bar code 66 or other printed indicia.

The masks described herein may be incorporated into the eye of a patientin different ways. For example, as discussed in more detail below inconnection with FIG. 49, the mask 34 may be provided as a contact lensplaced on the surface of the eyeball 10. Alternatively, the mask 34 maybe incorporated in an artificial intraocular lens designed to replacethe original lens 14 of the patient. Preferably, however, the mask 34 isprovided as a corneal implant or inlay, where it is physically insertedbetween the layers of the cornea 12.

When used as a corneal implant, layers of the cornea 12 are peeled awayto allow insertion of the mask 34. Typically, the optical surgeon (usinga laser) cuts away and peels away a flap of the overlying cornealepithelium. The mask 34 is then inserted and the flap is placed back inits original position where, over time, it grows back and seals theeyeball. In some embodiments, the mask 34 is attached or fixed to theeye 10 by support strands 72 and 74 shown in FIG. 40 and generallydescribed in U.S. Pat. No. 4,976,732, incorporated by reference hereinin its entirety.

In certain circumstances, to accommodate the mask 34, the surgeon may berequired to remove additional corneal tissue. Thus, in one embodiment,the surgeon may use a laser to peel away additional layers of the cornea12 to provide a pocket that will accommodate the mask 34. Application ofthe mask 34 to the cornea 12 of the eye 10 of a patient is described ingreater detail in connection with FIGS. 50A-51C.

Removal of the mask 34 may be achieved by simply making an additionalincision in the cornea 12, lifting the flap and removing the mask 34.Alternatively, ablation techniques may be used to completely remove themask 34.

FIGS. 41 and 42 illustrate another embodiment, of a mask 34 y thatincludes a coiled strand 80 of a fibrous or other material. Strand 80 iscoiled over itself to form the mask 34 y, which may therefore bedescribed as a spiral-like mask. This arrangement provides a pinhole oraperture 38 y substantially in the center of the mask 34 y. The mask 34y can be removed by a technician or surgeon who grasps the strand 80with tweezers 82 through an opening made in a flap of the corneal 12.FIG. 42 shows this removal technique.

Further mask details are disclosed in U.S. Pat. No. 4,976,732, issuedDec. 11, 1990 and in U.S. patent application Ser. No. 10/854,033, filedMay 26, 2004, both of which are incorporated by reference herein intheir entirety.

III. Preferred UV-Resistant Polymeric Mask Materials

Because the mask has a very high surface to volume ratio and is exposedto a great deal of sunlight following implantation, the mask preferablycomprises a material which has good resistance to degradation, includingfrom exposure to ultraviolet (UV) or other wavelengths of light.Polymers including a UV absorbing component, including those comprisingUV absorbing additives or made with UV absorbing monomers (includingco-monomers), may be used in forming masks as disclosed herein which areresistant to degradation by UV radiation. Examples of such polymersinclude, but are not limited to, those described in U.S. Pat. Nos.4,985,559 and 4,528,311, the disclosures of which are herebyincorporated by reference in their entireties. In a preferredembodiment, the mask comprises a material which itself is resistant todegradation by UV radiation. In one embodiment, the mask comprises apolymeric material which is substantially reflective of or transparentto UV radiation.

Alternatively, the mask may include a component which imparts adegradation resistive effect, or may be provided with a coating,preferably at least on the anterior surface, which imparts degradationresistance. Such components may be included, for example, by blendingone or more degradation resistant polymers with one or more otherpolymers. Such blends may also comprise additives which providedesirable properties, such as UV absorbing materials. In one embodiment,blends preferably comprise a total of about 1-20 wt. %, including about1-10 wt. %, 5-15 wt. %, and 10-20 wt. % of one or more degradationresistant polymers. In another embodiment, blends preferably comprise atotal of about 80-100 wt. %, including about 80-90 wt. %, 85-95 wt. %,and 90-100 wt. % of one or more degradation resistant polymers. Inanother embodiment, the blend has more equivalent proportions ofmaterials, comprising a total of about 40-60 wt. %, including about50-60 wt. %, and 40-50 wt. % of one or more degradation resistantpolymers. Masks may also include blends of different types ofdegradation resistant polymers, including those blends comprising one ormore generally UV transparent or reflective polymers with one or morepolymers incorporating UV absorption additives or monomers. These blendsinclude those having a total of about 1-20 wt. %, including about 1-10wt. %, 5-15 wt. %, and 10-20 wt. % of one or more generally UVtransparent polymers, a total of about 80-100 wt. %, including about80-90 wt. %, 85-95 wt. %, and 90-100 wt. % of one or more generally UVtransparent polymers, and a total of about 40-60 wt. %, including about50-60 wt. %, and 40-50 wt. % of one or more generally UV transparentpolymers. The polymer or polymer blend may be mixed with other materialsas discussed below, including, but not limited to, opacification agents,polyanionic compounds and/or wound healing modulator compounds. Whenmixed with these other materials, the amount of polymer or polymer blendin the material which makes up the mask is preferably about 50%-99% byweight, including about 60%-90% by weight, about 65-85% by weight, about70-80% by weight, and about 90-99% by weight.

Preferred degradation resistant polymers include halogenated polymers.Preferred halogenated polymers include fluorinated polymers, that is,polymers having at least one carbon-fluorine bond, including highlyfluorinated polymers. The term “highly fluorinated” as it is usedherein, is a broad term used in its ordinary sense, and includespolymers having at least one carbon-fluorine bond (C—F bond) where thenumber of C—F bonds equals or exceeds the number of carbon-hydrogenbonds (C—H bonds). Highly fluorinated materials also includeperfluorinated or fully fluorinated materials, materials which includeother halogen substituents such as chlorine, and materials which includeoxygen- or nitrogen-containing functional groups. For polymericmaterials, the number of bonds may be counted by referring to themonomer(s) or repeating units which form the polymer, and in the case ofa copolymer, by the relative amounts of each monomer (on a molar basis).

Preferred highly fluorinated polymers include, but are not limited to,polytetrafluoroethylene (PFTE or Teflon®), polyvinylidene fluoride (PVDFor Kynar®), poly-1,1,2-trifluoroethylene, and perfluoroalkoxyethylene(PFA). Other highly fluorinated polymers include, but are not limitedto, homopolymers and copolymers including one or more of the followingmonomer units: tetrafluoroethylene —(CF₂-CF₂)−; vinylidene fluoride—(CF₂—CH₂)—; 1,1,2-trifluoroethylene —(CF₂—CHF)—; hex afluoropropene—(CF(CF₃)—CF₂)—; vinyl fluoride —(CH₂—CHF)— (homopolymer is not “highlyfluorinated”); oxygen-containing monomers such as —(O—CF₂)—,—(O—CF₂—CF₂)—, —(O—CF(CF₃)—CF₂)—; chlorine-containing monomers such as—(CF₂—CFCl)—. Other fluorinated polymers, such as fluorinated polyimideand fluorinated acrylates, having sufficient degrees of fluorination arealso contemplated as highly fluorinated polymers for use in masksaccording to preferred embodiments. The homopolymers and copolymersdescribed herein are available commercially and/or methods for theirpreparation from commercially available materials are widely publishedand known to those in the polymer arts.

Although highly fluorinated polymers are preferred, polymers having oneor more carbon-fluorine bonds but not falling within the definition of“highly fluorinated” polymers as discussed above, may also be used. Suchpolymers include co-polymers formed from one or more of the monomers inthe preceding paragraph with ethylene, vinyl fluoride or other monomerto form a polymeric material having a greater number of C—H bonds thanC—F bonds. Other fluorinated polymers, such as fluorinated polyimide,may also be used. Other materials that could be used in someapplications, alone or in combination with a fluorinated or a highlyfluorinated polymer, are described in U.S. Pat. No. 4,985,559 and inU.S. Pat. No. 4,538,311, both of which are hereby incorporated byreference herein in their entirety.

The preceding definition of highly fluorinated is best illustrated bymeans of a few examples. One preferred UV-resistant polymeric materialis polyvinylidene fluoride (PVDF), having a structure represented by theformula: —(CF₂—CH₂)_(n)—. Each repeating unit has two C—H bonds, and twoC—F bonds. Because the number of C—F bonds equals or exceeds the numberof C—H bonds, PVDF homopolymer is a “highly fluorinated” polymer.Another material is a tetrafluoroethylene/vinyl fluoride copolymerformed from these two monomers in a 2:1 molar ratio. Regardless ofwhether the copolymer formed is block, random or any other arrangement,from the 2:1 tetrafluoroethylene:vinyl fluoride composition one canpresume a “repeating unit” comprising two tetrafluoroethylene units,each having four C—F bonds, and one vinyl fluoride unit having three C—Hbonds and one C—F bond. The total bonds for two tetrafluoroethylenes andone vinyl fluoride are nine C—F bonds, and three C—H bonds. Because thenumber of C—F bonds equals or exceeds the number of C—H bonds, thiscopolymer is considered highly fluorinated.

Certain highly fluorinated polymers, such as PVDF, have one or moredesirable characteristics, such as being relatively chemically inert andhaving a relatively high UV transparency as compared to theirnon-fluorinated or less highly fluorinated counterpart polymers.Although the applicant does not intend to be bound by theory, it ispostulated that the electronegativity of fluorine may be responsible formany of the desirable properties of the materials having relativelylarge numbers of C—F bonds.

In preferred embodiments, at least a portion of the highly fluorinatedpolymer material forming the mask comprises an opacification agent whichimparts a desired degree of opacity. In one embodiment, theopacification agent provides sufficient opacity to produce the depth offield improvements described herein, e.g., in combination with atransmissive aperture. In one embodiment, the opacification agentrenders the material opaque. In another embodiment, the opacificationagent prevents transmission of about 90 percent or more of incidentlight. In another embodiment, the opacification agent renders thematerial opaque. In another embodiment, the opacification agent preventstransmission of about 80 percent or more of incident light. Preferredopacification agents include, but are not limited to organic dyes and/orpigments, preferably black ones, such as azo dyes, hematoxylin black,and Sudan black; inorganic dyes and/or pigments, including metal oxidessuch as iron oxide black and ilminite, silicon carbide and carbon (e.g.carbon black, submicron powdered carbon). The foregoing materials may beused alone or in combination with one or more other materials. Theopacification agent may be applied to one or more surfaces of the maskon all or some of the surface, or it may be mixed or combined with thepolymeric material (e.g. blended during the polymer melt phase).Although any of the foregoing materials may be used, carbon has beenfound to be especially useful in that it does not fade over time as domany organic dyes, and that it also aids the UV stability of thematerial by absorbing UV radiation In one embodiments, carbon may bemixed with polyvinylidene fluoride (PVDF) or other polymer compositioncomprising highly fluorinated polymer such that the carbon comprisesabout 2% to about 20% by weight of the resulting composition, includingabout 10% to about 15% by weight, including about 12%, about 13%, andabout 14% by weight of the resulting composition.

Some opacification agents, such pigments, which are added to blacken,darken or opacity portions of the mask may cause the mask to absorbincident radiation to a greater degree than mask material not includingsuch agents. Because the matrix polymer that carries or includes thepigments may be subject to degradation from the absorbed radiation, itis preferred that the mask, which is thin and has a high surface areamaking it vulnerable to environmental degradation, be made of a materialwhich is itself resistant to degradation such as from UV radiation, orthat it be generally transparent to or non-absorbing of UV radiation.Use of a highly UV resistant and degradation resistant material, such asPVDF, which is highly transparent to UV radiation, allows for greaterflexibility in choice of opacification agent because possible damage tothe polymer caused by selection of a particular opacification agent isgreatly reduced.

A number of variations of the foregoing embodiments of degradationresistant constructions are contemplated. In one variation, a mask ismade almost exclusively of a material that is not subject to UVdegradation. For example, the mask can be made of a metal, a highlyfluorinated polymer, or another similar material. Construction of themask with metal is discussed in more detail in U.S. application Ser. No.11/000,562 filed Dec. 1, 2004 and entitled “Method of Making an OcularImplant” and also in U.S. application Ser. No. 11/107,359 filed Apr. 14,2005 with the title “Method of Making an Ocular Implant”, both of whichare incorporated herein in their entirety by reference. As used in thiscontext, “exclusively” is a broad term that allows for the presence ofsome non-functional materials (e.g., impurities) and for anopacification agent, as discussed above. In other embodiments, the maskcan include a combination of materials. For example, in one variation,the mask is formed primarily of any implantable material and is coatedwith a UV resistant material. In another variation, the mask includesone or more UV degradation inhibitors and/or one or more UV degradationresistant polymers in sufficient concentration such that the mask undernormal use conditions will maintain sufficient functionality in terms ofdegradation to remain medically effective for at least about 5 years,preferably at least about 10 years, and in certain implementations atleast about 20 years.

FIG. 54 is a flow chart illustrating one method for making a mask from acomposition comprising a highly fluorinated polymer and an opacificationagent. At step 2000, a liquid form of a polymer is created by dissolvingpolyvinylidene fluoride (PVDF) pellets into a solvent such as DimethylAcetamide (DMAC or DMA) using heat until the PVDF has completelydissolved. In one embodiment, the solution may be mixed for a minimum of12 hours to ensure that the PVDF has completely dissolved. At step 2200,the PVDF/DMAC solution is mixed with an opacification agent, such ascarbon black, using a high speed shear mixer. In one embodiment, thecarbon black comprises 13% by weight of the resulting composition whilethe PVDF comprises 87% by weight of the resulting composition. At step2300, the PVDF/carbon black solution is milled in a high speed mill, forexample an Eiger high speed mill, to break up any large carbonagglomerates in the solution. The PVDF/carbon black solution may be runthrough the mill a second time to further break up any carbonagglomerates. At step 2400, the resulting solution is applied to asilicone wafer to create a polymer film on the silicone disk. Here,approximately 55 g of the PVDF/carbon black solution is poured into adispensing barrel for application on a silicone wafer. The silicone diskis placed on the spinner of a spin casting machine and the dispensingbarrel is used to apply a bead of PVDF/carbon black solution to thesilicone wafer in a circular pattern, leaving the center 1″ diameter ofthe disk empty. The spinner cycle is actuated to disperse thePVDF/carbon black solution over the disk, forming a uniform 10 micronthick film. The coated silicone disk is then placed on a hot-plate toevaporate the DMAC. At step 2500, the coated silicon e wafer is placedunder an Eximer laser. A laser cutting mask is mounted in the laser andthe laser is actuated. Using the laser cutting mask, approximately 150corneal mask patterns are laser machined into the PVDF/carbon blackfilm. The corneal mask patterns are arranged such that the materialextending approximately 5 mm from the edge of the silicon disk is notused. During the laser machining, the silicone disk may be bathed inNitrogen gas in order to cool the surface. At step 2600, the lasermachined masks are removed from the silicone disk using a razor bladeand placed into the bottom half of a convex Teflon forming mold. The tophalf of the Teflon forming mold is placed on top of the mask and themolds placed in an oven at about 160° C. At step 2700, the molds areheated and baked to cure the masks. The molds are allowed to bake forapproximately two hours at approximately 160° C. After two hours theoven temperature is reduced to about 30° C. and the masks are baked forapproximately two hours or until the oven temperature has dropped tobelow around 40° C.

IV. Additives to Reduce Corneal Deposits and/or Promote Proper Healing

In some circumstances, corneal implants are associated with deposits onthe cornea. Loading of one or more polyanionic compounds into thepolymeric material of a corneal implant may reduce and/or substantiallyeliminate deposits on the cornea, possibly by attracting and/orretaining growth factors.

In a preferred embodiment the one or more polyanionic compounds includecarbohydrates, proteins, natural proteoglycans, and/or theglycosaminoglycan moieties of proteoglycans, as well as derivatives(such as sulfated derivatives) and salts of compounds such as those inthe aforementioned categories. Preferred polyanionic compounds includeone or more of dermatan sulfate, chondroitin sulfate, keratan sulfate,heparan sulfate, heparin, dextran sulfate, hyaluronic acid, pentosanpolysulfate, xanthan, carrageenan, fibronectin, laminin, chondronectin,vitronectin, poly L-lysine salts, and anionic, preferably sulfated,carbohydrates such as alginate may also be used, as well as salts andderivatives of the listed compounds. Examples of preferred anioniccompounds and combinations of polyanionic compounds include keratansulfate/chrondroitin sulfate-proteoglycan, dermatan sulfateproteoglycan, and dextran sulfate.

In one embodiment, a polyanionic compound comprises acidic sulfatemoieties and the sulfur content is greater than about 5% by weight,preferably greater than about 10% by weight. In an even more preferredembodiment, the average molecular weight of a polyanionic compound isabout 40,000 to 500,000 Daltons.

In a preferred embodiment, the total weight of the one or morepolyanionic compounds in the loaded polymeric material is about 0.1% byweight to about 50% by weight, including about 5% by weight to about 20%by weight, about 12% by weight to about 17% by weight, about 0.5% byweight to about 4% by weight, and about 5% by weight to about 15% byweight. It should be noted that the percentages recited herein inrelation to polyanionic compounds, opacification agents and woundhealing modulator compounds are percent by weight with 100% being thetotal weight of the entire mask composition including all additives.

In one embodiment, the body of the mask is formed from a polymericmaterial having one or more polyanionic compounds loaded therein.Loading of a polyanionic compound is performed by mixing the polyanioniccompound with the resin and any other additives of the polymericmaterial prior to molding or casting of the body of the mask. Althoughsome of a polyanionic compound that is loaded into the polymericmaterial may be on the surface of the mask, loading is to bedistinguished from coating in that a coated material would not havepolyanionic material throughout the bulk of the mask.

The loaded polymeric material is preferably made by suspending ordissolving polymer, one or more polyanionic compounds and any otheradditives (such as wound healing modulators, as described below) in asolvent or solvent system, and then casting a film whereby the solventor solvent system is removed such as by evaporation. Preferred castingmethods include spin casting and other methods, including those known inthe art, which can form a thin material of relatively even thickness.Although other methods of making thin substrates, such as extrusion, maybe used, solvent casting is generally preferred because it does not needto be done at high temperatures that may cause degradation of somepolyanionic compounds. The polymer, polyanionic compound, and/or otheradditives may be ground or milled, such as by ball milling, to reducethe particle size of the material prior to suspending, dissolving ormelting as part of making the mask.

In methods using solvent casting, preferred solvents include those whichare capable of dissolving the polymeric material, polyanionic compounds,and/or other additives. A suitable solvent or solvent system (i.e.combination of two or more solvents) may be chosen by one skilled in theart based upon known solubilities for a given polymeric material and/orroutine experimentation based upon chemical principles. In solventcasting methods, the temperature of the solvent or solution should be nohigher than the boiling point of the solvent or solvent system, and ispreferably about 10° C. to about 70° C. During or after casting of thesolution to form a film, the temperature may be elevated, includingabove the boiling point.

In one embodiment, a mask, such as an inlay, comprising PVDF, dextransulfate, and carbon was made by spin casting. 100 grams of PVDC (about71% by weight) in the form of pellets was dissolved in 400 grams ofdimethylacetamide. 17 grams of carbon (about 12% by weight) and 24 gramsof dextran sulfate (about 17% by weight) are ball milled to reduceparticle size and then added to the PVDF/DMA solution. The percentagesby weight are the percentages of the solids portion, that is the portionthat is not the solvent. The solution was at room temperature(approximately 17° C. to about 25° C.). The solution was then spin castto form a film.

In one embodiment, the device includes a wound healing modulator. Whenpresent, the wound healing modulator is on at least one surface or itmay be loaded into the polymeric material. A wound healing modulator isdefined as a compound that assists in proper healing of a wound, such asby increasing the rate of healing, decreasing inflammation, moderatingor suppressing immune response, decreasing scarring, decreasing cellproliferation, reducing infection, encouraging transdifferentiation ofkeratocytes into cells that lay down collagen, and the like. Woundhealing modulators include, without limitation, antibiotics,antineoplastics including antimitotics, antimetabolics and antibiotictypes, anti-inflammatories, immunosupressants, and antifungals.Preferred compounds include, but are not limited to, fluorouracil,mitomycin C, paclitaxel, NSAIDs (e.g. ibuprofen, naproxen, flurbiprofen,carprofen, suprofen, ketoprofen), and cyclosporins. Other preferredcompounds include proteoglycans, glycosaminoglycans, and salts andderivatives thereof, as well as other carbohydrates and/or proteins,including those disclosed above.

A wound healing modulator may be included in the mask by loading it intothe polymeric material as discussed above with respect to thepolyanionic compounds. It may also be included by binding it to one ormore surfaces of the device. The “binding” of the wound healingmodulator to the device may occur by phenomena that do not generallyinvolve chemical bonds, including adsorption, hydrogen bonding, van derWaals forces, electrostatic attraction, ionic bonding, and the like, orit may occur by phenomena that do include chemical bonds. In a preferredembodiment, the total weight of the one or more wound healing modulatorcompounds in the loaded polymeric material is about 0.1% by weight toabout 50% by weight, including about 5% by weight to about 20% byweight, about 12% by weight to about 17% by weight, about 0.5% by weightto about 4% by weight, and about 5% by weight to about 15% by weight.

In one embodiment, carbon, gold or other material on a surface of themask acts as an adsorbent or otherwise participates in the binding ofone or more wound healing modulators to the implant. The material on thesurface of the mask that participates in binding the wound healingmodulator may be part of the bulk material of the implant (distributedthroughout the implant or which migrates to the surface during and/orfollowing formation of the implant) and/or deposited on a surface of themask, such as an opacification agent as described elsewhere infra. Theimplant is then exposed to one or more wound healing modulators, such asby dipping in a solution (including dispersions and emulsions)comprising at least one wound healing modulator, to allow wound healingmodulator(s) to bind to the implant. The solvent used to assist inapplying and binding the wound healing modulator to the implant ispreferably biocompatible, does not leave a harmful residue, and/or doesnot cause dissolution or swelling of the polymeric material of the mask.If more than one wound healing modulator is used, binding may beperformed by dipping in a single solution containing all desired woundhealing modulators or by dipping the implant in two or more successivesolutions, each of which contains one or more of the desired woundhealing modulators. The process of binding wound healing modulator tothe implant may be done at any time. In one embodiment, at least some ofthe wound healing modulator is bound to the implant as part of themanufacturing process. In another embodiment, a medical practitioner,such as an ophthalmologist, binds at least some of the wound healingmodulator to the implant just prior to implantation.

In alternate embodiments, one or more wound healing modulators are boundto the implant using any suitable method for binding drugs or otheruseful compounds to implants and medical devices and/or using methodsfor making drug delivery devices which deliver a drug locally in thearea of implantation or placement over a period of time.

V. Masks Configured to Reduce Visibile Diffraction Patterns

Many of the foregoing masks can be used to improve the depth of focus ofa patient. Various additional mask embodiments are discussed below. Someof the embodiments described below include nutrient transport structuresthat are configured to enhance or maintain nutrient flow betweenadjacent tissues by facilitating transport of nutrients across the mask.The nutrient transport structures of some of the embodiments describedbelow are configured to at least substantially prevent nutrientdepletion in adjacent tissues. The nutrient transport structures candecrease negative effects due to the presence of the mask in adjacentcorneal layers when the mask is implanted in the cornea, increasing thelongevity of the masks. The inventors have discovered that certainarrangements of nutrient transport structures generate diffractionpatterns that interfere with the vision improving effect of the masksdescribed herein. Accordingly, certain masks are described herein thatinclude nutrient transport structures that do not generate diffractionpatterns or otherwise interfere with the vision enhancing effects of themask embodiments.

FIGS. 43-44 show one embodiment of a mask 100 configured to increasedepth of focus of an eye of a patient suffering from presbyopia. Themask 100 is similar to the masks hereinbefore described, except asdescribed differently below. The mask 100 can be made of the materialsdiscussed herein, including those discussed in Section III. Also, themask 100 can be formed by any suitable process, such as those discussedbelow in connection with FIGS. 48 a-48 d with variations of suchprocesses. The mask 100 is configured to be applied to an eye of apatient, e.g., by being implanted in the cornea of the patient. The mask100 may be implanted within the cornea in any suitable manner, such asthose discussed above in connection with FIGS. 50A-51C.

In one embodiment, the mask 100 includes a body 104 that has an anteriorsurface 108 and a posterior surface 112. In one embodiment, the body 104is capable of substantially maintaining natural nutrient flow betweenthe first corneal layer and the second corneal layer. In one embodiment,the material is selected to maintain at least about ninety-six percentof the natural flow of at least one nutrient (e.g., glucose) between afirst corneal layer (e.g., the layer 1210) and a second corneal layer(e.g., the layer 1220). The body 104 may be formed of any suitablematerial, including at least one of an open cell foam material, anexpanded solid material, and a substantially opaque material. In oneembodiment, the material used to form the body 104 has relatively highwater content.

In one embodiment, the mask 100 includes and a nutrient transportstructure 116. The nutrient transport structure 116 may comprise aplurality of holes 120. The holes 120 are shown on only a portion of themask 100, but the holes 120 preferably are located throughout the body104 in one embodiment. In one embodiment, the holes 120 are arranged ina hex pattern, which is illustrated by a plurality of locations 120′ inFIG. 45A. As discussed below, a plurality of locations may be definedand later used in the later formation of a plurality of holes 120 on themask 100. The mask 100 has an outer periphery 124 that defines an outeredge of the body 104. In some embodiments, the mask 100 includes anaperture 128 at least partially surrounded by the outer periphery 124and a non-transmissive portion 132 located between the outer periphery124 and the aperture 128.

Preferably the mask 100 is symmetrical, e.g., symmetrical about a maskaxis 136. In one embodiment, the outer periphery 124 of the mask 100 iscircular. The masks in general have has a diameter within the range offrom about 3 mm to about 8 mm, often within the range of from about 3.5mm to about 6 mm, and less than about 6 mm in one embodiment. In anotherembodiment, the mask is circular and has a diameter in the range of 4 to6 mm. In another embodiment, the mask 100 is circular and has a diameterof less than 4 mm. The outer periphery 124 has a diameter of about 3.8mm in another embodiment. In some embodiments, masks that areasymmetrical or that are not symmetrical about a mask axis providebenefits, such as enabling a mask to be located or maintained in aselected position with respect to the anatomy of the eye.

The body 104 of the mask 100 may be configured to coupled with aparticular anatomical region of the eye. The body 104 of the mask 100may be configured to conform to the native anatomy of the region of theeye in which it is to be applied. For example, where the mask 100 is tobe coupled with an ocular structure that has curvature, the body 104 maybe provided with an amount of curvature along the mask axis 136 thatcorresponds to the anatomical curvature. For example, one environment inwhich the mask 100 may be deployed is within the cornea of the eye of apatient. The cornea has an amount of curvature that varies from personto person about a substantially constant mean value within anidentifiable group, e.g., adults. When applying the mask 100 within thecornea, at least one of the anterior and posterior surfaces 108, 112 ofthe mask 100 may be provided with an amount of curvature correspondingto that of the layers of the cornea between which the mask 100 isapplied.

In some embodiments, the mask 100 has a desired amount of optical power.Optical power may be provided by configuring the at least one of theanterior and posterior surfaces 108, 112 with curvature. In oneembodiment, the anterior and posterior surfaces 108, 112 are providedwith different amounts of curvature. In this embodiment, the mask 100has varying thickness from the outer periphery 124 to the aperture 128.

In one embodiment, one of the anterior surface 108 and the posteriorsurface 112 of the body 104 is substantially planar. In one planarembodiment, very little or no uniform curvature can be measured acrossthe planar surface. In another embodiment, both of the anterior andposterior surfaces 108, 112 are substantially planar. In general, thethickness of the inlay may be within the range of from about 1 micron toabout 40 micron, and often in the range of from about 5 micron to about20 micron. In one embodiment, the body 104 of the mask 100 has athickness 138 of between about 5 micron and about 10 micron. In oneembodiment, the thickness 138 of the mask 100 is about 5 micron. Inanother embodiment, the thickness 138 of the mask 100 is about 8 micron.In another embodiment, the thickness 138 of the mask 100 is about 10micron.

Thinner masks generally are more suitable for applications wherein themask 100 is implanted at a relatively shallow location in (e.g., closeto the anterior surface of) the cornea. In thinner masks, the body 104may be sufficiently flexible such that it can take on the curvature ofthe structures with which it is coupled without negatively affecting theoptical performance of the mask 100. In one application, the mask 100 isconfigured to be implanted about 5 um beneath the anterior surface ofthe cornea. In another application, the mask 100 is configured to beimplanted about 52 um beneath the anterior surface of the cornea. Inanother application, the mask 100 is configured to be implanted about125 um beneath the anterior surface of the cornea. Further detailsregarding implanting the mask 100 in the cornea are discussed above inconnection with FIGS. 50A-51C.

A substantially planar mask has several advantages over a non-planarmask. For example, a substantially planar mask can be fabricated moreeasily than one that has to be formed to a particular curvature. Inparticular, the process steps involved in inducing curvature in the mask100 can be eliminated. Also, a substantially planar mask may be moreamenable to use on a wider distribution of the patient population (oramong different sub-groups of a broader patient population) because thesubstantially planar mask uses the curvature of each patient's cornea toinduce the appropriate amount of curvature in the body 104.

In some embodiments, the mask 100 is configured specifically for themanner and location of coupling with the eye. In particular, the mask100 may be larger if applied over the eye as a contact lens or may besmaller if applied within the eye posterior of the cornea, e.g.,proximate a surface of the lens of the eye. As discussed above, thethickness 138 of the body 104 of the mask 100 may be varied based onwhere the mask 100 is implanted. For implantation at deeper levelswithin the cornea, a thicker mask may be advantageous. Thicker masks areadvantageous in some applications. For example, they are generallyeasier to handle, and therefore are easier to fabricate and to implant.Thicker masks may benefit more from having a preformed curvature thanthinner masks. A thicker mask could be configured to have little or nocurvature prior to implantation if it is configured to conform to thecurvature of the native anatomy when applied.

The aperture 128 is configured to transmit substantially all incidentlight along the mask axis 136. The non-transmissive portion 132surrounds at least a portion of the aperture 128 and substantiallyprevents transmission of incident light thereon. As discussed inconnection with the above masks, the aperture 128 may be a through-holein the body 104 or a substantially light transmissive (e.g.,transparent) portion thereof. The aperture 128 of the mask 100 generallyis defined within the outer periphery 124 of the mask 100. The aperture128 may take any of suitable configurations, such as those describedabove in connection with FIGS. 6-42.

In one embodiment, the aperture 128 is substantially circular and issubstantially centered in the mask 100. The size of the aperture 128 maybe any size that is effective to increase the depth of focus of an eyeof a patient suffering from presbyopia. For example, the aperture 128can be circular, having a diameter of less than about 2.2 mm in oneembodiment. In another embodiment, the diameter of the aperture isbetween about 1.8 mm and about 2.2 mm. In another embodiment, theaperture 128 is circular and has a diameter of about 1.8 mm or less. Inanother embodiment, the diameter of the aperture is about 1.6 mm. Mostapertures will have a diameter within the range of from about 1.0 mm toabout 2.5 mm, and often within the range of from about 1.3 mm to about1.9 mm.

The non-transmissive portion 132 is configured to prevent transmissionof radiant energy through the mask 100. For example, in one embodiment,the non-transmissive portion 132 prevents transmission of substantiallyall of at least a portion of the spectrum of the incident radiantenergy. In one embodiment, the non-transmissive portion 132 isconfigured to prevent transmission of substantially all visible light,e.g., radiant energy in the electromagnetic spectrum that is visible tothe human eye. The non-transmissive portion 132 may substantiallyprevent transmission of radiant energy outside the range visible tohumans in some embodiments.

As discussed above in connection with FIG. 3, preventing transmission oflight through the non-transmissive portion 132 decreases the amount oflight that reaches the retina and the fovea that would not converge atthe retina and fovea to form a sharp image. As discussed above inconnection with FIG. 4, the size of the aperture 128 is such that thelight transmitted therethrough generally converges at the retina orfovea. Accordingly, a much sharper image is presented to the eye thanwould otherwise be the case without the mask 100.

In one embodiment, the non-transmissive portion 132 preventstransmission of about 90 percent of incident light. In anotherembodiment, the non-transmissive portion 132 prevents transmission ofabout 92 percent of all incident light. The non-transmissive portion 132of the mask 100 may be configured to be opaque to prevent thetransmission of light. As used herein the term “opaque” is intended tobe a broad term meaning capable of preventing the transmission ofradiant energy, e.g., light energy, and also covers structures andarrangements that absorb or otherwise block all or less than all or atleast a substantial portion of the light. In one embodiment, at least aportion of the body 104 is configured to be opaque to more than 99percent of the light incident thereon.

As discussed above, the non-transmissive portion 132 may be configuredto prevent transmission of light without absorbing the incident light.For example, the mask 100 could be made reflective or could be made tointeract with the light in a more complex manner, as discussed in U.S.Pat. No. 6,551,424, issued Apr. 29, 2003, which is hereby incorporatedby reference herein in its entirety.

As discussed above, the mask 100 also has a nutrient transport structurethat in some embodiments comprises the plurality of holes 120. Thepresence of the plurality of holes 120 (or other transport structure)may affect the transmission of light through the non-transmissiveportion 132 by potentially allowing more light to pass through the mask100. In one embodiment, the non-transmissive portion 132 is configuredto absorb about 99 percent or more of the incident light from passingthrough the mask 100 without holes 120 being present. The presence ofthe plurality of holes 120 allows more light to pass through thenon-transmissive portion 132 such that only about 92 percent of thelight incident on the non-transmissive portion 132 is prevented frompassing through the non-transmissive portion 132. The holes 120 mayreduce the benefit of the aperture 128 on the depth of focus of the eyeby allowing more light to pass through the non-transmissive portion tothe retina.

Reduction in the depth of focus benefit of the aperture 128 due to theholes 120 is balanced by the nutrient transmission benefits of the holes120. In one embodiment, the transport structure 116 (e.g., the holes120) is capable of substantially maintaining natural nutrient flow froma first corneal layer (i.e., one that is adjacent to the anteriorsurface 108 of the mask 100) to the second corneal layer (i.e., one thatis adjacent to the posterior surface 112 of the mask 100). The pluralityof holes 120 are configured to enable nutrients to pass through the mask100 between the anterior surface 108 and the posterior surface 112. Asdiscussed above, the holes 120 of the mask 100 shown in FIG. 43 may belocated anywhere on the mask 100. Other mask embodiments describedherein below locate substantially all of the nutrient transportstructure in one or more regions of a mask.

The holes 120 of FIG. 43 extends at least partially between the anteriorsurface 108 and the posterior surface 112 of the mask 100. In oneembodiment, each of the holes 120 includes a hole entrance 140 and ahole exit 164. The hole entrance 140 is located adjacent to the anteriorsurface 108 of the mask 100. The hole exit 164 is located adjacent tothe posterior surface 112 of the mask 100. In one embodiment, each ofthe holes 120 extends the entire distance between the anterior surface108 and the posterior surface 112 of the mask 100.

The transport structure 116 is configured to maintain the transport ofone or more nutrients across the mask 100. The transport structure 116of the mask 100 provides sufficient flow of one or more nutrients acrossthe mask 100 to prevent depletion of nutrients at least at one of thefirst and second corneal layers (e.g., the layers 1210 and 1220). Onenutrient of particular importance to the viability of the adjacentcorneal layers is glucose. The transport structure 116 of the mask 100provides sufficient flow of glucose across the mask 100 between thefirst and second corneal layers to prevent glucose depletion that wouldharm the adjacent corneal tissue. Thus, the mask 100 is capable ofsubstantially maintaining nutrient flow (e.g., glucose flow) betweenadjacent corneal layers. In one embodiment, the nutrient transportstructure 116 is configured to prevent depletion of more than about 4percent of glucose (or other biological substance) in adjacent tissue ofat least one of the first corneal layer and the second corneal layer.

The holes 120 may be configured to maintain the transport of nutrientsacross the mask 100. In one embodiment, the holes 120 are formed with adiameter of about 0.015 mm or more. In another embodiment, the holeshave a diameter of about 0.020 mm. In another embodiment, the holes havea diameter of about 0.025 mm. In another embodiment, the holes have adiameter of about 0.027 mm. In another embodiment, the holes 120 have adiameter in the range of about 0.020 mm to about 0.029 mm. The number ofholes in the plurality of holes 120 is selected such that the sum of thesurface areas of the hole entrances 140 of all the holes 100 comprisesabout 5 percent or more of surface area of the anterior surface 108 ofthe mask 100. In another embodiment, the number of holes 120 is selectedsuch that the sum of the surface areas of the hole exits 164 of all theholes 120 comprises about 5 percent or more of surface area of theposterior surface 112 of the mask 100. In another embodiment, the numberof holes 120 is selected such that the sum of the surface areas of thehole exits 164 of all the holes 120 comprises about 5 percent or more ofsurface area of the posterior surface 112 of the mask 112 and the sum ofthe surface areas of the hole entrances 140 of all the holes 120comprises about 5 percent or more of surface area of the anteriorsurface 108 of the mask 100. In another embodiment, the plurality ofholes 120 may comprise about 1600 microperforations.

Each of the holes 120 may have a relatively constant cross-sectionalarea. In one embodiment, the cross-sectional shape of each of the holes120 is substantially circular. Each of the holes 120 may comprise acylinder extending between the anterior surface 108 and the posteriorsurface 112.

The relative position of the holes 120 is of interest in someembodiments. As discussed above, the holes 120 of the mask 100 arehex-packed, e.g., arranged in a hex pattern. In particular, in thisembodiment, each of the holes 120 is separated from the adjacent holes120 by a substantially constant distance, sometimes referred to hereinas a hole pitch. In one embodiment, the hole pitch is about 0.045 mm.

In a hex pattern, the angles between lines of symmetry are approximately43 degrees. The spacing of holes along any line of holes is generallywithin the range of from about 30 microns to about 100 microns, and, inone embodiment, is approximately 43 microns. The hole diameter isgenerally within the range of from about 10 microns to about 100microns, and in one embodiment, is approximately 20 microns. The holespacing and diameter are related if you want to control the amount oflight coming through. The light transmission is a function of the sum ofhole areas as will be understood by those of skill in the art in view ofthe disclosure herein.

The embodiment of FIG. 43 advantageously enables nutrients to flow fromthe first corneal layer to the second corneal layer. The inventors havediscovered that negative visual effects can arise due to the presence ofthe transport structure 116. For example, in some cases, a hex packedarrangement of the holes 120 can generate diffraction patterns visibleto the patient. For example, patients might observe a plurality ofspots, e.g., six spots, surrounding a central light with holes 120having a hex patterned.

The inventors have discovered a variety of techniques that produceadvantageous arrangements of a transport structure such that diffractionpatterns and other deleterious visual effects do not substantiallyinhibit other visual benefits of a mask. In one embodiment, wherediffraction effects would be observable, the nutrient transportstructure is arranged to spread the diffracted light out uniformlyacross the image to eliminate observable spots. In another embodiment,the nutrient transport structure employs a pattern that substantiallyeliminates diffraction patterns or pushes the patterns to the peripheryof the image.

FIG. 45B-45C show two embodiments of patterns of holes 220 that may beapplied to a mask that is otherwise substantially similar to the mask100. The holes 220 of the hole patterns of FIGS. 45B-45C are spaced fromeach other by a random hole spacing or hole pitch. In other embodimentsdiscussed below, holes are spaced from each other by a non-uniformamount, e.g., not a random amount. In one embodiment, the holes 220 havea substantially uniform shape (cylindrical shafts having a substantiallyconstant cross-sectional area). FIG. 45C illustrates a plurality ofholes 220 separated by a random spacing, wherein the density of theholes is greater than that of FIG. 45B. Generally, the higher thepercentage of the mask body that has holes the more the mask willtransport nutrients in a manner similar to the native tissue. One way toprovide a higher percentage of hole area is to increase the density ofthe holes. Increased hole density can also permit smaller holes toachieve the same nutrient transport as is achieved by less dense, largerholes.

FIG. 46A shows a portion of another mask 200 a that is substantiallysimilar to the mask 100, except described differently below. The mask200 a can be made of the materials discussed herein, including thosediscussed in Section III. The mask 200 a can be formed by any suitableprocess, such as those discussed below in connection with FIGS. 48 a-48d and with variations of such processes. The mask 200 a has a nutrienttransport structure 216 a that includes a plurality of holes 220 a. Asubstantial number of the holes 220 a have a non-uniform size. The holes220 a may be uniform in cross-sectional shape. The cross-sectional shapeof the holes 220 a is substantially circular in one embodiment. Theholes 220 a may be circular in shape and have the same diameter from ahole entrance to a hole exit, but are otherwise non-uniform in at leastone aspect, e.g., in size. It may be preferable to vary the size of asubstantial number of the holes by a random amount. In anotherembodiment, the holes 220 a are non-uniform (e.g., random) in size andare separated by a non-uniform (e.g., a random) spacing.

FIG. 46B illustrates another embodiment of a mask 200 b that issubstantially similar to the mask 100, except as described differentlybelow. The mask 200 b can be made of the materials discussed herein,including those discussed in Section III. Also, the mask 200 b can beformed by any suitable process, such as those discussed below inconnection with FIGS. 48 a-48 d and with variations of such processes.The mask 200 b includes a body 204 b. The mask 200 b has a transportstructure 216 b that includes a plurality of holes 220 b with anon-uniform facet orientation. In particular, each of the holes 220 bhas a hole entrance that may be located at an anterior surface of themask 200 b. A facet of the hole entrance is defined by a portion of thebody 204 b of the mask 200 b surrounding the hole entrance. The facet isthe shape of the hole entrance at the anterior surface. In oneembodiment, most or all the facets have an elongate shape, e.g., anoblong shape, with a long axis and a short axis that is perpendicular tothe long axis. The facets may be substantially uniform in shape. In oneembodiment, the orientation of facets is not uniform. For example, asubstantial number of the facets may have a non-uniform orientation. Inone arrangement, a substantial number of the facets have a randomorientation. In some embodiments, the facets are non-uniform (e.g.,random) in shape and are non-uniform (e.g., random) in orientation.

Other embodiments may be provided that vary at least one aspect,including one or more of the foregoing aspects, of a plurality of holesto reduce the tendency of the holes to produce visible diffractionpatterns or patterns that otherwise reduce the vision improvement thatmay be provided by a mask with an aperture, such as any of thosedescribed above. For example, in one embodiment, the hole size, shape,and orientation of at least a substantial number of the holes may bevaried randomly or may be otherwise non-uniform.

FIG. 47 shows another embodiment of a mask 300 that is substantiallysimilar to any of the masks hereinbefore described, except as describeddifferently below. The mask 300 can be made of the materials discussedherein, including those discussed in Section III. Also, the mask 300 canbe formed by any suitable process, such as those discussed below inconnection with FIGS. 48 a-48 d and with variations of such processes.The mask 300 includes a body 304. The body 304 has an outer peripheralregion 305, an inner peripheral region 306, and a hole region 307. Thehole region 307 is located between the outer peripheral region 305 andthe outer peripheral region 306. The body 304 may also include anaperture region, where the aperture (discussed below) is not a throughhole. The mask 300 also includes a nutrient transport structure 316. Inone embodiment, the nutrient transport structure includes a plurality ofholes. At least a substantial portion of the holes (e.g., all of theholes) are located in the hole region 307. As above, only a portion ofthe nutrient structure 316 is shown for simplicity. But it should beunderstood that the hole may be located through the hole region 307.

The outer peripheral region 305 may extend from an outer periphery 324of the mask 300 to a selected outer circumference 326 of the mask 300.The selected outer circumference 325 of the mask 300 is located aselected radial distance from the outer periphery 324 of the mask 300.In one embodiment, the selected outer circumference 325 of the mask 300is located about 0.05 mm from the outer periphery 324 of the mask 300.

The inner peripheral region 306 may extend from an inner location, e.g.,an inner periphery 326 adjacent an aperture 328 of the mask 300 to aselected inner circumference 327 of the mask 300. The selected innercircumference 327 of the mask 300 is located a selected radial distancefrom the inner periphery 326 of the mask 300. In one embodiment, theselected inner circumference 327 of the mask 300 is located about 0.05mm from the inner periphery 326.

The mask 300 may be the product of a process that involves randomselection of a plurality of locations and formation of holes on the mask300 corresponding to the locations. As discussed further below, themethod can also involve determining whether the selected locationssatisfy one or more criteria. For example, one criterion prohibits all,at least a majority, or at least a substantial portion of the holes frombeing formed at locations that correspond to the inner or outerperipheral regions 305, 306. Another criterion prohibits all, at least amajority, or at least a substantial portion of the holes from beingformed too close to each other. For example, such a criterion could beused to assure that a wall thickness, e.g., the shortest distancebetween adjacent holes, is not less than a predetermined amount. In oneembodiment, the wall thickness is prevented from being less than about20 microns.

In a variation of the embodiment of FIG. 47, the outer peripheral region305 is eliminated and the hole region 307 extends from the innerperipheral region 306 to an outer periphery 324. In another variation ofthe embodiment of FIG. 47, the inner peripheral region 306 is eliminatedand the hole region 307 extends from the outer peripheral region 305 toan inner periphery 326.

FIG. 44B shows a mask 400 that is similar to the mask 100 except asdescribed differently below. The mask 400 can be made of the materialsdiscussed herein, including those discussed in Section III. The mask 400can be formed by any suitable process, such as those discussed below inconnection with FIGS. 48 a-48 d and with variations of such processes.The mask 400 includes a body 404 that has an anterior surface 408 and aposterior surface 412. The mask 400 also includes a nutrient transportstructure 4316 that, in one embodiment, includes a plurality of holes420. The holes 420 are formed in the body 404 so that nutrient transportis provided but transmission of radiant energy (e.g., light) to theretinal locations adjacent the fovea through the holes 404 issubstantially prevented. In particular, the holes 404 are formed suchthat when the eye with which the mask 1000 is coupled is directed at anobject to be viewed, light conveying the image of that object thatenters the holes 420 cannot exit the holes along a path ending near thefovea.

In one embodiment, each of the holes 420 has a hole entrance 460 and ahole exit 464. Each of the holes 420 extends along a transport axis 466.The transport axis 466 is formed to substantially prevent propagation oflight from the anterior surface 408 to the posterior surface 412 throughthe holes 420. In one embodiment, at least a substantial number of theholes 420 have a size to the transport axis 466 that is less than athickness of the mask 400. In another embodiment, at least a substantialnumber of the holes 420 have a longest dimension of a perimeter at leastat one of the anterior or posterior surfaces 408, 412 (e.g., a facet)that is less than a thickness of the mask 400. In some embodiments, thetransport axis 466 is formed at an angle with respect to a mask axis 436that substantially prevents propagation of light from the anteriorsurface 408 to the posterior surface 412 through the hole 420. Inanother embodiment, the transport axis 466 of one or more holes 420 isformed at an angle with respect to the mask axis 436 that is largeenough to prevent the projection of most of the hole entrance 460 fromoverlapping the hole exit 464.

In one embodiment, the hole 420 is circular in cross-section and has adiameter between about 0.5 micron and about 8 micron and the transportaxis 466 is between 5 and 85 degrees. The length of each of the holes420 (e.g., the distance between the anterior surface 408 and theposterior surface 412) is between about 8 and about 92 micron. Inanother embodiment, the diameter of the holes 420 is about 5 micron andthe transport angle is about 40 degrees or more. As the length of theholes 420 increases it may be desirable to include additional holes 420.In some cases, additional holes 420 counteract the tendency of longerholes to reduce the amount of nutrient flow through the mask 400.

FIG. 44C shows another embodiment of a mask 500 similar to the mask 100,except as described differently below. The mask 500 can be made of thematerials discussed herein, including those discussed in Section III.The mask 500 can be formed by any suitable process, such as thosediscussed below in connection with FIGS. 48 a-48 d and with variationsof such processes. The mask 500 includes a body 504 that has an anteriorsurface 508, a first mask layer 510 adjacent the anterior surface 508, aposterior surface 512, a second mask layer 514 adjacent the posteriorsurface 512, and a third mask layer 515 located between the first masklayer 510 and the second mask layer 514. The mask 500 also includes anutrient transport structure 516 that, in one embodiment, includes aplurality of holes 520. The holes 520 are formed in the body 504 so thatnutrient are transported across the mask, as discussed above, buttransmission of radiant energy (e.g., light) to retinal locationsadjacent the fovea through the holes 504 is substantially prevented. Inparticular, the holes 504 are formed such that when the eye with whichthe mask 500 is coupled is directed at an object to be viewed, lightconveying the image of that object that enters the holes 520 cannot exitthe holes along a path ending near the fovea.

In one embodiment, at least one of the holes 520 extends along anon-linear path that substantially prevents propagation of light fromthe anterior surface to the posterior surface through the at least onehole. In one embodiment, the mask 500 includes a first hole portion 520a that extends along a first transport axis 566 a, the second mask layer514 includes a second hole portion 520 b extending along a secondtransport axis 566 b, and the third mask layer 515 includes a third holeportion 520 c extending along a third transport axis 566 c. The first,second, and third transport axes 566 a, 566 b, 566 c preferably are notcollinear. In one embodiment, the first and second transport axes 566 a,566 b are parallel but are off-set by a first selected amount. In oneembodiment, the second and third transport axes 566 b, 566 c areparallel but are off-set by a second selected amount. In the illustratedembodiment, each of the transport axes 566 a, 566 b, 566 c are off-setby one-half of the width of the hole portions 520 a, 520 b, 520 c. Thus,the inner-most edge of the hole portion 520 a is spaced from the axis536 by a distance that is equal to or greater than the distance of theouter-most edge of the hole portion 520 b from the axis 536. Thisspacing substantially prevents light from passing through the holes 520from the anterior surface 508 to the posterior surface 512.

In one embodiment, the first and second amounts are selected tosubstantially prevent the transmission of light therethrough. The firstand second amounts of off-set may be achieved in any suitable fashion.One technique for forming the hole portions 520 a, 520 b, 520 c with thedesired off-set is to provide a layered structure. As discussed above,the mask 500 may include the first layer 510, the second layer 514, andthe third layer 515. FIG. 44C shows that the mask 500 can be formed withthree layers. In another embodiment, the mask 500 is formed of more thanthree layers. Providing more layers may advantageously further decreasethe tendency of light to be transmitted through the holes 490 onto theretina. This has the benefit of reducing the likelihood that a patientwill observe or otherwise perceive a patter that will detract from thevision benefits of the mask 500. A further benefit is that less lightwill pass through the mask 500, thereby enhancing the depth of focusincrease due to the pin-hole sized aperture formed therein.

In any of the foregoing mask embodiments, the body of the mask may beformed of a material selected to provide adequate nutrient transport andto substantially prevent negative optic effects, such as diffraction, asdiscussed above. In various embodiments, the masks are formed of an opencell foam material. In another embodiment, the masks are formed of anexpanded solid material.

As discussed above in connection with FIGS. 45B and 45C, various randompatterns of holes may advantageously be provided for nutrient transport.In some embodiment, it may be sufficient to provide regular patternsthat are non-uniform in some aspect. Non-uniform aspects to the holesmay be provided by any suitable technique.

In a first step of one technique, a plurality of locations 220′ isgenerated. The locations 220′ are a series of coordinates that maycomprise a non-uniform pattern or a regular pattern. The locations 220′may be randomly generated or may be related by a mathematicalrelationship (e.g., separated by a fixed spacing or by an amount thatcan be mathematically defined). In one embodiment, the locations areselected to be separated by a constant pitch or spacing and may be hexpacked.

In a second step, a subset of the locations among the plurality oflocations 220′ is modified to maintain a performance characteristic ofthe mask. The performance characteristic may be any performancecharacteristic of the mask. For example, the performance characteristicmay relate to the structural integrity of the mask. Where the pluralityof locations 220′ is selected at random, the process of modifying thesubset of locations may make the resulting pattern of holes in the maska “pseudo-random” pattern.

Where a hex packed pattern of locations (such as the locations 120′ ofFIG. 45A) is selected in the first step, the subset of locations may bemoved with respect to their initial positions as selected in the firststep. In one embodiment, each of the locations in the subset oflocations is moved by an amount equal to a fraction of the hole spacing.For example, each of the locations in the subset of locations may bemoved by an amount equal to one-quarter of the hole spacing. Where thesubset of locations is moved by a constant amount, the locations thatare moved preferably are randomly or pseudo-randomly selected. Inanother embodiment, the subset of location is moved by a random or apseudo-random amount.

In one technique, an outer peripheral region is defined that extendsbetween the outer periphery of the mask and a selected radial distanceof about 0.05 mm from the outer periphery. In another embodiment, aninner peripheral region is defined that extends between an aperture ofthe mask and a selected radial distance of about 0.05 mm from theaperture. In another embodiment, an outer peripheral region is definedthat extends between the outer periphery of the mask and a selectedradial distance and an inner peripheral region is defined that extendsbetween the aperture of the mask and a selected radial distance from theaperture. In one technique, the subset of location is modified byexcluding those locations that would correspond to holes formed in theinner peripheral region or the outer peripheral region. By excludinglocations in at least one of the outer peripheral region and the innerperipheral region, the strength of the mask in these regions isincreased. Several benefits are provided by stronger inner and outerperipheral regions. For example, the mask may be easier to handle duringmanufacturing or when being applied to a patient without causing damageto the mask.

In another embodiment, the subset of locations is modified by comparingthe separation of the holes with minimum and or maximum limits. Forexample, it may be desirable to assure that no two locations are closerthan a minimum value. In some embodiments this is important to assurethat the wall thickness, which corresponds to the separation betweenadjacent holes, is no less than a minimum amount. As discussed above,the minimum value of separation is about 20 microns in one embodiment,thereby providing a wall thickness of no less than about 20 microns.

In another embodiment, the subset of locations is modified and/or thepattern of location is augmented to maintain an optical characteristicof the mask. For example, the optical characteristic may be opacity andthe subset of locations may be modified to maintain the opacity of anon-transmissive portion of a mask. In another embodiment, the subset oflocations may be modified by equalizing the density of holes in a firstregion of the body compared with the density of holes in a second regionof the body. For example, the locations corresponding to the first andsecond regions of the non-transmissive portion of the mask may beidentified. In one embodiment, the first region and the second regionare arcuate regions (e.g., wedges) of substantially equal area. A firstareal density of locations (e.g., locations per square inch) iscalculated for the locations corresponding to the first region and asecond areal density of locations is calculated for the locationscorresponding to the second region. In one embodiment, at least onelocation is added to either the first or the second region based on thecomparison of the first and second areal densities. In anotherembodiment, at least one location is removed based on the comparison ofthe first and second areal densities.

The subset of locations may be modified to maintain nutrient transportof the mask. In one embodiment, the subset of location is modified tomaintain glucose transport.

In a third step, a hole is formed in a body of a mask at locationscorresponding to the pattern of locations as modified, augmented, ormodified and augmented. The holes are configured to substantiallymaintain natural nutrient flow from the first layer to the second layerwithout producing visible diffraction patterns.

VI. Methods of Applying Pinhole Aperture Devices

The various masks discussed herein can be used to improve the vision ofa presbyopic patient as well as patient's with other vision problems.The masks discussed herein can be deployed in combination with a LASIKprocedure, to eliminate the effects of abrasions, aberrations, anddivots in the cornea. It is also believed that the masks disclosedherein can be used to treat patients suffering from maculardegeneration, e.g., by directing light rays to unaffected portions ofretina, thereby improving the vision of the patient. Whatever treatmentis contemplated, more precise alignment of the central region of a maskthat has a pin-hole aperture with the line of sight or visual axis ofthe patient is believed to provide greater clinical benefit to thepatient. Other ocular devices that do not require a pin-hole aperturecan also benefit from the alignment techniques discussed below. Also,various structures and techniques that can be used to remove an oculardevices are discussed below.

A. Alignment of the Pinhole Aperture with the Patient's Visual Axis

Alignment of the central region of the pinhole aperture 38, inparticular, the optical axis 39 of the mask 34 with the visual axis ofthe eye 10 may be achieved in a variety of ways. In one technique, anoptical device employs input from the patient to locate the visual axisin connection with a procedure to implant the mask 34. This technique isdescribed in more detail in U.S. patent application Ser. No. 11/000,562,filed Dec. 1, 2004, the entire contents of which is hereby expresslyincorporated by reference herein.

In other embodiments, systems and methods identify one or more visibleocular features that correlate to the line of sight. The one or morevisible ocular feature(s) is observed while the mask is being applied tothe eye. Alignment using a visible ocular feature enables the mask toperform adequately to increase depth of focus. In some applications, atreatment method enhances the correlation of the visible ocular featureand the line of sight to maintain or improve alignment of the mask axisand the line of sight.

Accurate alignment of the mask is believed to improve the clinicalbenefit of the mask. However, neither the optical axis of the mask northe line of sight of the patient is generally visible during thesurgical procedures contemplated for implanting masks. However,substantial alignment of the optical axis of the mask and the line ofsight may be achieved by aligning a visible feature of the mask with avisible feature of the eye, e.g., a visible ocular feature. As usedherein, the term “visible ocular feature” is a broad term that includesfeatures viewable with a viewing aid, such as a surgical microscope orloupes, as well as those visible to the unaided eye. Various methods arediscussed below that enhance the accuracy of the placement of the maskusing a visible ocular feature. These methods generally involve treatingthe eye to increase the correlation between the location of the visibleocular feature and the line of sight or to increase the visibility ofthe ocular feature.

FIG. 48 is a flow chart illustrating one method of aligning a mask withan axis of the eye using a visible ocular feature. The method mayinclude a step of identifying a visible ocular feature, a combination ofvisible ocular features, or a combination of a visible ocular featureand an optical effect that sufficiently correlate with the location ofthe line of sight of the eye. In one technique the entrance pupil orother visible ocular feature could be used alone to estimate thelocation of the line of sight. In another technique, the location of theline of sight can be estimated to be located between, e.g., half-waybetween, the center of the entrance pupil and the first Purkinje image.Other estimates can be based on a combination of two or more of thefirst Purkinje image, the second Purkinje image, the third Purkinjeimage, and the fourth Purkinje image. Other estimates can be based onone or more Purkinje image and one or more other anatomical features. Inanother technique, the location of the line of sight can be estimated asbeing located at the center of the pupil if the first Purkinje image islocated close to the center of the entrance pupil. A single Purkinjeimage may provide an adequate estimate of the location of the line ofsight if the Purkinje image is generated by a beam having a fixed or aknow angle of incidence relative to a surface of the eye. The method mayalso include a step of identifying a visible feature of the mask to bealigned with a visible ocular feature, as discussed further below.

In a step 1000, an eye is treated to affect or alter, preferablytemporarily, a visible ocular feature. In some embodiments, the featureof the eye is altered to increase the correlation of the location of theocular feature to the line of sight of the eye. In some cases, thetreatment of step 1000 enhances the visibility of the ocular feature tothe surgeon. The ocular feature may be any suitable feature, such as thepupil or any other feature that correlates or can be altered by atreatment to correlate with the line of sight of the patient. Sometechniques involve the alignment of a feature of a mask with the pupilor a portion of the pupil. One technique for enhancing the visibility ofthe pupil or the correlation of the location of the pupil with the lineof sight involves manipulating the size of the pupil, e.g., increasingor decreasing the pupil size.

In connection with the method of FIG. 48, any suitable criteria can beused to confirm alignment of an eye and a mask with a pin-hole aperture.For example, the mask can be considered aligned with the eye when anyfeature of the mask is aligned with any anatomical landmark on the eyeso that an axis passing through the center of the pin-hole aperture isco-linear with or substantially co-linear with an optical axis of theeye, such as the line of sight and an axis passing through the center ofthe entrance pupil and the center of the eyeball. As used herein,“anatomical landmark” is a broad term that includes an visible ocularfeature, such as the center of the entrance pupil, the intersection ofthe line of sight with a selected corneal layer, the inner periphery ofthe iris, the outer periphery of the iris, the inner periphery of thesclera, the boundary between the iris and the pupil, the boundarybetween the iris and the sclera, the location of the first Purkinjeimage, the location of the second Purkinje image, the location of thethird Purkinje image, the location of the fourth Purkinje image, therelative position of any combination of Purkinje images, the combinationof the location of a Purkinje image and any other anatomical landmark,and any combination of the foregoing or other anatomical feature.

The pupil size may be decreased by any suitable technique, includingpharmacologic manipulation and light manipulation. One agent used inpharmacologic manipulation of pupil size is pilocarpine. Pilocarpinereduces the size of the pupil when applied to the eye. One technique forapplying pilocarpine is to inject an effective amount into the eye.Other agents for reducing pupil size include: carbachol, demecarium,isoflurophate, physostigmine, aceclidine, and echothiophate.

Pilocarpine is known to shift the location of the pupil nasally in somecases. This can be problematic for some ocular procedures, e.g., thoseprocedures directed at improving distance vision. The applicant hasdiscovered, however, that such a shift does not significantly reduce theefficacy of the masks described herein.

While the alignment of the masks described herein with the line of sightis not significantly degraded by the use of pilocarpine, an optionalstep of correcting for the nasal shift of the pupil may be performed.

In one variation, the treatment of the step 1000 involves increasingpupil size. This technique may be more suitable where it is desired toalign a visible mask feature near an outer periphery of the mask withthe pupil. These techniques are discussed further below.

As discussed above, the treatment of the step 1000 can involvenon-pharmacologic techniques for manipulating a visible ocular feature.One non-pharmacologic technique involves the use of light to cause thepupil size to change. For example, a bright light can be directed intothe eye to cause the pupil to constrict. This approach may substantiallyavoid displacement of the pupil that has been observed in connectionwith some pharmacologic techniques. Light can also be used to increasepupil size. For example, the ambient light can be reduced to cause thepupil to dilate. A dilated pupil may provide some advantages inconnection with aligning to a visible mask feature adjacent to an outerperiphery of a mask, as discussed below.

In a step 1004, a visible feature of a mask is aligned with the ocularfeature identified in connection with step 1000. As discussed above, themask may have an inner periphery, an outer periphery, and a pin-holeaperture located within the inner periphery. The pin-hole aperture maybe centered on a mask axis. Other advantageous mask features discussedabove may be included in masks applied by the methods illustrated byFIG. 48. For example, such features may include nutrient transportstructures configured to substantially eliminate diffraction patterns,structures configured to substantially prevent nutrient depletion inadjacent corneal tissue, and any other mask feature discussed above inconnection with other masks.

One technique involves aligning at least a portion of the innerperiphery of a mask with an anatomical landmark. For example, the innerperiphery of the mask could be aligned with the inner periphery of theiris. This may be accomplished using unaided vision or a viewing aid,such as loupes or a surgical microscope. The mask could be aligned sothat substantially the same spacing is provided between the innerperiphery of the mask and the inner periphery of the iris. Thistechnique could be facilitated by making the iris constrict, asdiscussed above. A viewing aid may be deployed to further assist inaligning the mask to the anatomical landmark. For example, a viewing aidcould include a plurality of concentric markings that the surgeon canuse to position the mask. Where the inner periphery of the iris issmaller than the inner periphery of the mask, a first concentric markingcan be aligned with the inner periphery of the iris and the mask couldbe positioned so that a second concentric marking is aligned with theinner periphery of the mask. The second concentric marking would befarther from the common center than the first concentric marking in thisexample.

In another technique, the outer periphery of the mask could be alignedwith an anatomical landmark, such as the inner periphery of the iris.This technique could be facilitated by dilating the pupil. Thistechnique may be enhanced by the use of a viewing aid, which couldinclude a plurality of concentric markings, as discussed above. Inanother technique, the outer periphery of the mask could be aligned withan anatomical landmark, such as the boundary between the iris and thesclera. This technique may be facilitated by the use of a viewing aid,such as a plurality of concentric markings.

In another technique, the mask can be aligned so that substantially thesame spacing is provided between the inner periphery of the mask and theinner periphery of the iris. In this technique, the pupil preferably isconstricted so that the diameter of the pupil is less than the diameterof the pin-hole aperture.

Alternatively, an artifact can be formed in the mask that gives a visualcue of proper alignment. For example, there could be one or more windowportions formed in the mask through which the edge of the pupil could beobserved. The window portions could be clear graduations or they couldbe at least partially opaque regions through which the pupil could beobserved. In one technique, the surgeon moves the mask until the pupilcan be seen in corresponding window portions on either side of thepin-hole aperture. The window portions enable a surgeon to align avisible ocular feature located beneath a non-transparent section of themask with a feature of the mask. This arrangement enables alignmentwithout a great amount of pupil constriction, e.g., where the pupil isnot fully constricted to a size smaller than the diameter of the innerperiphery.

Preferably the alignment of the ocular feature with one or more visiblemask features causes the mask axis to be substantially aligned with theline of sight of the eye. “Substantial alignment” of the mask axis withthe eye, e.g., with the line of sight of the eye (and similar terms,such as “substantially collinear”) can be said to have been achievedwhen a patient's vision is improved by the implantation of the mask. Insome cases, substantial alignment can be said to have been achieved whenthe mask axis is within a circle centered on the line of sight andhaving a radius no more than 5 percent of the radius of the innerperiphery of the mask. In some cases, substantial alignment can be saidto have been achieved when the mask axis is within a circle centered onthe line of sight and having a radius no more than 10 percent of theradius of the inner periphery of the mask. In some cases, substantialalignment can be said to have been achieved when the mask axis is withina circle centered on the line of sight and having a radius no more than15 percent of the radius of the inner periphery of the mask. In somecases, substantial alignment can be said to have been achieved when themask axis is within a circle centered on the line of sight and having aradius no more than 20 percent of the radius of the inner periphery ofthe mask. In some cases, substantial alignment can be said to have beenachieved when the mask axis is within a circle centered on the line ofsight and having a radius no more than 25 percent of the radius of theinner periphery of the mask. In some cases, substantial alignment can besaid to have been achieved when the mask axis is within a circlecentered on the line of sight and having a radius no more than 30percent of the radius of the inner periphery of the mask. As discussedabove, the alignment of the mask axis and the line of sight of thepatient is believed to enhance the clinical benefit of the mask.

In a step 1008, the mask is applied to the eye of the patient.Preferably the alignment of the optical axis of the mask and the line ofsight of the patient is maintained while the mask is applied to the eyeof the patient. In some cases, this alignment is maintained bymaintaining the alignment of a mask feature, e.g., a visible maskfeature, and a pupil feature, e.g., a visible pupil feature. Forexample, one technique maintains the alignment of at least one of theinner periphery and the outer periphery of the mask and the pupil whilethe mask is being applied to the eye of the patient.

As discussed above, a variety of techniques are available for applying amask to the eye of a patient. Any suitable technique of applying a maskmay be employed in connection with the method illustrated in FIG. 48.For example, as set forth above in connection with FIGS. 50A-51C,various techniques may be employed to position the mask at differentdepths or between different layers within the cornea. In particular, inone technique, a corneal flap of suitable depth is hinged open. Thedepth of the flap is about the outermost 20% of the thickness of thecornea in one technique. In another technique, the depth of the flap isabout the outermost 10% of the thickness of the cornea. In anothertechnique, the depth of the flap is about the outermost 5% of thethickness of the cornea. In another technique, the depth of the flap isin the range of about the outermost 5% to about the outermost 10% of thethickness of the cornea. In another technique, the depth of the flap isin the range of about the outermost 5% to about the outermost 20% of thethickness of the cornea. Other depths and ranges are possible for othertechniques.

Thereafter, in one technique, the mask is placed on a layer of thecornea such that at least one of the inner periphery and the outerperiphery of the mask is at a selected position relative to the pupil.In variations on this technique, other features of the mask may bealigned with other ocular features. Thereafter, the hinged corneal flapis placed over the mask.

Additional techniques for applying a mask are discussed above inconnection with FIGS. 52A-53. These methods may be modified for use inconnection with alignment using visible features. These techniquesenable the mask to be initially placed on the corneal layer that islifted from the eye. The initial placement of the mask on the liftedcorneal layer may be before or after alignment of a visible ocularfeature with a visible mask feature. In some techniques, primary andsecondary alignment steps are performed before and after the initialplacement of the mask on the lifted corneal layer.

Many additional variations of the foregoing methods are also possible.The alignment methods involving alignment of visible features may becombined with any of the techniques discussed above in connection withoptically locating the patient's line of sight. One technique involvesremoving an epithelial sheet and creating a depression in the Bowman'smembrane or in the stroma. Also, the mask can be placed in a channelformed in the cornea, e.g., in or near the top layers of the stroma.Another useful technique for preparing the cornea involves the formationof a pocket within the cornea. These methods related to preparation ofthe cornea are described in greater detail above.

Some techniques may benefit from the placement of a temporarypost-operative covering, such as a contact lens or other covering, overthe flap until the flap has healed. In one technique, a covering isplaced over the flap until an epithelial sheet adheres to the mask orgrows over an exposed layer, such as the Bowman's membrane.

B. Methods of Applying a Mask

Having described method for locating the visual axis of the eye 10 or avisible ocular feature that indicates the location thereof, and forvisually marking the visual axis, various methods for applying a mask tothe eye will be discussed.

FIG. 49 shows one technique for screening a patient interested inincreasing his or her depth of focus. The process begins at step 1100,in which the patient is fitted with soft contact lenses, i.e., a softcontact lens is placed in each of the patient's eyes. If needed, thesoft contact lenses may include vision correction. Next, at step 1110,the visual axis of each of the patient's eyes is located as describedabove. At a step 1120, a mask, such as any of those described above, isplaced on the soft contact lenses such that the optical axis of theaperture of the mask is aligned with the visual axis of the eye. In thisposition, the mask will be located generally concentric with thepatient's pupil. In addition, the curvature of the mask should parallelthe curvature of the patient's cornea. The process continues at a step1130, in which the patient is fitted with a second set of soft contactlenses, i.e., a second soft contact lens is placed over the mask in eachof the patient's eyes. The second contact lens holds the mask in asubstantially constant position. Last, at step 1140, the patient'svision is tested. During testing, it is advisable to check thepositioning of the mask to ensure that the optical axis of the apertureof the mask is substantially collinear with the visual axis of the eye.Further details of testing are set forth in U.S. Pat. No. 6,551,424,issued Apr. 29, 2003, incorporated by reference herein in its entirety.

In accordance with a still further embodiment of the invention, a maskis surgically implanted into the eye of a patient interested inincreasing his or her depth of focus. For example, a patient may sufferfrom presbyopia, as discussed above. The mask may be a mask as describedherein, similar to those described in the prior art, or a mask combiningone or more of these properties. Further, the mask may be configured tocorrect visual aberrations. To aid the surgeon surgically implanting amask into a patient's eye, the mask may be pre-rolled or folded for easeof implantation.

The mask may be implanted in several locations. For example, the maskmay be implanted underneath the cornea's epithelium sheet, beneath thecornea's Bowman membrane, in the top layer of the cornea's stroma, or inthe cornea's stroma. When the mask is placed underneath the cornea'sepithelium sheet, removal of the mask requires little more than removalof the cornea's epithelium sheet.

FIGS. 50 a through 50 c show a mask 1200 inserted underneath anepithelium sheet 1210. In this embodiment, the surgeon first removes theepithelium sheet 1210. For example, as shown in FIG. 50 a, theepithelium sheet 1210 may be rolled back. Then, as shown in FIG. 50 b,the surgeon creates a depression 1215 in a Bowman's membrane 420corresponding to the visual axis of the eye. The visual axis of the eyemay be located as described above and may be marked by use of thealignment apparatus 1200 or other similar apparatus. The depression 1215should be of sufficient depth and width to both expose the top layer1230 of the stroma 1240 and to accommodate the mask 1200. The mask 1200is then placed in the depression 1215. Because the depression 1215 islocated in a position to correspond to the visual axis of the patient'seye, the central axis of the pinhole aperture of the mask 1200 will besubstantially collinear with the visual axis of the eye. This willprovide the greatest improvement in vision possible with the mask 1200.Last, the epithelium sheet 1210 is placed over the mask 1200. Over time,as shown in FIG. 50 c, the epithelium sheet 1210 will grow and adhere tothe top layer 1230 of the stroma 1240, as well as the mask 1200depending, of course, on the composition of the mask 1200. As needed, acontact lens may be placed over the incised cornea to protect the mask.

FIGS. 51 a through 51 c show a mask 1300 inserted beneath a Bowman'smembrane 1320 of an eye. In this embodiment, as shown in FIG. 51 a, thesurgeon first hinges open the Bowman's membrane 1320. Then, as shown inFIG. 51 b, the surgeon creates a depression 1315 in a top layer 1300 ofa stroma 1340 corresponding to the visual axis of the eye. The visualaxis of the eye may be located as described above and may be marked byany suitable technique, for example using a visible ocular feature or atechnique employing patient input. The depression 1315 should be ofsufficient depth and width to accommodate the mask 1300. Then, the mask1300 is placed in the depression 1315. Because the depression 1315 islocated in a position to correspond to the visual axis of the patient'seye, the central axis of the pinhole aperture of the mask 1300 will besubstantially collinear with the visual axis of the eye. This willprovide the greatest improvement in vision possible with the mask 1300.Last, the Bowman's membrane 1320 is placed over the mask 1300. Overtime, as shown in FIG. 51 c, the epithelium sheet 1310 will grow overthe incised area of the Bowman's membrane 1320. As needed, a contactlens may be placed over the incised cornea to protect the mask.

In another embodiment, a mask of sufficient thinness, i.e., less thansubstantially 20 microns, may be placed underneath epithelium sheet1210. In another embodiment, a mask or an optic having a thickness lessthan about 20 microns may be placed beneath Bowman's membrane 1320without creating a depression in the top layer of the stroma.

In an alternate method for surgically implanting a mask in the eye of apatient, the mask may be threaded into a channel created in the toplayer of the stroma. In this method, a curved channeling tool creates achannel in the top layer of the stroma, the channel being in a planeparallel to the surface of the cornea. The channel is formed in aposition corresponding to the visual axis of the eye. The channelingtool either pierces the surface of the cornea or, in the alternative, isinserted via a small superficial radial incision. In the alternative, alaser focusing an ablative beam may create the channel in the top layerof the stroma. In this embodiment, the mask may be a single segment witha break, or it may be two or more segments. In any event, the mask inthis embodiment is positioned in the channel and is thereby located sothat the central axis of the pinhole aperture formed by the mask issubstantially collinear with the patient's visual axis to provide thegreatest improvement in the patient's depth of focus.

In another alternate method for surgically implanting a mask in the eyeof a patient, the mask may be injected into the top layer of the stroma.In this embodiment, an injection tool with a stop penetrates the surfaceof the cornea to the specified depth. For example, the injection toolmay be a ring of needles capable of producing a mask with a singleinjection. In the alternative, a channel may first be created in the toplayer of the stroma in a position corresponding to the visual axis ofthe patient. Then, the injector tool may inject the mask into thechannel. In this embodiment, the mask may be a pigment, or it may bepieces of pigmented material suspended in a bio-compatible medium. Thepigment material may be made of a polymer or, in the alternative, madeof a suture material. In any event, the mask injected into the channelis thereby positioned so that the central axis of the pinhole apertureformed by the pigment material is substantially collinear with thevisual axis of the patient.

In another method for surgically implanting a mask in the eye of apatient, the mask may be placed beneath the corneal flap created duringkeratectomy, when the outermost 20% of the cornea is hinged open. Aswith the implantation methods discussed above, a mask placed beneath thecorneal flap created during keratectomy should be substantially alignedwith the patient's visual axis, as discussed above, for greatest effect.

In another method for surgically implanting a mask in the eye of apatient, the mask may be aligned with the patient's visual axis andplaced in a pocket created in the cornea's stroma.

Further details concerning alignment apparatuses are disclosed in U.S.application Ser. No. 10/854,032, filed May 26, 2004, incorporated byreference herein in its entirety. Further variations on techniquesinvolving pharmacologic manipulation for alignment or other purposes arediscussed in U.S. application Ser. No. 11/257,505, filed Oct. 24, 2005,which is hereby incorporated by reference herein in its entirety.

VII. Further Methods of Treating a Patient

As discussed above in, various techniques are particularly suited fortreating a patient by applying masks such as those disclosed herein toan eye. For example, in some techniques, a visual cue in the form of aprojected image for a surgeon is provided during a procedure forapplying a mask. In addition, some techniques for treating a patientinvolve positioning an implant with the aid of a marked reference point.These methods are illustrated by FIGS. 52-53B.

In one method, a patient is treated by placing an implant 1400 in acornea 1404. A corneal flap 1408 is lifted to expose a surface in thecornea 1404 (e.g., an intracorneal surface). Any suitable tool ortechnique may be used to lift the corneal flap 1408 to expose a surfacein the cornea 1404. For example, a blade (e.g., a microkeratome), alaser or an electrosurgical tool could be used to form a corneal flap. Areference point 1412 on the cornea 1404 is identified. The referencepoint 1412 thereafter is marked in one technique, as discussed furtherbelow. The implant 1400 is positioned on the intracorneal surface. Inone embodiment, the flap 1408 is then closed to cover at least a portionof the implant 1400.

The surface of the cornea that is exposed is a stromal surface in onetechnique. The stromal surface may be on the corneal flap 1408 or on anexposed surface from which the corneal flap 1408 is removed.

The reference point 1412 may be identified in any suitable manner. Forexample, the alignment devices and methods described above may be usedto identify the reference point 1412. In one technique, identifying thereference point 1412 involves illuminating a light spot (e.g., a spot oflight formed by all or a discrete portion of radiant energycorresponding to visible light, e.g., red light). As discussed above,the identifying of a reference point may further include placing liquid(e.g., a fluorescein dye or other dye) on the intracorneal surface.Preferably, identifying the reference point 1412 involves alignmentusing any of the techniques described herein.

As discussed above, various techniques may be used to mark an identifiedreference point. In one technique the reference point is marked byapplying a dye to the cornea or otherwise spreading a material withknown reflective properties onto the cornea. As discussed above, the dyemay be a substance that interacts with radiant energy to increase thevisibility of a marking target or other visual cue. The reference pointmay be marked by a dye with any suitable tool. The tool is configured sothat it bites into a corneal layer, e.g., an anterior layer of theepithelium, and delivers a thin ink line into the corneal layer in oneembodiment. The tool may be made sharp to bite into the epithelium. Inone application, the tool is configured to deliver the dye as discussedabove upon being lightly pressed against the eye. This arrangement isadvantageous in that it does not form a larger impression in the eye. Inanother technique, the reference point may be marked by making animpression (e.g., a physical depression) on a surface of the cornea withor without additional delivery of a dye.

In another technique, the reference point may be marked by illuminatinga light or other source of radiant energy, e.g., a marking targetilluminator and projecting that light onto the cornea (e.g., byprojecting a marking target).

Any of the foregoing techniques for marking a reference point may becombined with techniques that make a mark that indicates the location ofan axis of the eye, e.g., the visual axis or line-of-sight of the eye.In one technique, a mark indicates the approximate intersection of thevisual axis and a surface of the cornea. In another technique, a mark ismade approximately radially symmetrically disposed about theintersection of the visual axis and a surface of the cornea.

As discussed above, some techniques involve making a mark on anintracorneal surface. The mark may be made by any suitable technique. Inone technique a mark is made by pressing an implement against theinstracorneal surface. The implement may form a depression that has asize and shape that facilitate placement of a mask. For example, in oneform the implement is configured to form a circular ring (e.g., a thinline of dye, or a physical depression, or both) with a diameter that isslightly larger than the outer diameter of a mask to be implanted. Thecircular ring can be formed to have a diameter between about 4 mm andabout 5 mm. The intracorneal surface is on the corneal flap 1408 in onetechnique. In another technique, the intracorneal surface is on anexposed surface of the cornea from which the flap was removed. Thisexposed surface is sometimes referred to as a tissue bed.

In another technique, the corneal flap 1408 is lifted and thereafter islaid on an adjacent surface 1416 of the cornea 1404. In anothertechnique, the corneal flap 1408 is laid on a removable support 1420,such as a sponge. In one technique, the removable support has a surface1424 that is configured to maintain the native curvature of the cornealflap 1408.

FIG. 52 shows that the marked reference point 1412 is helpful inpositioning an implant on an intracorneal surface. In particular, themarked reference point 1412 enables the implant to be positioned withrespect to the visual axis of the eye. In the illustrated embodiment,the implant 1400 is positioned so that a centerline of the implant,indicated as M_(CL) extends through the marked reference point 1412.

FIG. 52A illustrates another technique wherein a reference 1412′ is aring or other two dimensional mark. In such a case, the implant 1400 maybe placed so that an outer edge of the implant and the ring correspond,e.g., such that the ring and the implant 1400 share the same orsubstantially the same center. Preferably, the ring and the implant 1400are aligned so that the centerline of the implant M_(CL) is on the lineof sight of the eye, as discussed above. The ring is shown in dashedlines because in the illustrated technique, it is formed on the anteriorsurface of the corneal flap 1408.

In one technique, the corneal flap 1408 is closed by returning thecorneal flap 1408 to the cornea 1404 with the implant 1400 on thecorneal flap 1408. In another technique, the corneal flap 1408 is closedby returning the corneal flap 1408 to the cornea 1404 over the implant1400, which previously was placed on the tissue bed (the exposedintracorneal surface).

When the intracorneal surface is a stromal surface, the implant 1400 isplaced on the stromal surface. At least a portion of the implant 1400 iscovered. In some techniques, the implant 1400 is covered by returning aflap with the implant 1400 thereon to the cornea 1404 to cover thestromal surface. In one technique, the stromal surface is exposed bylifting an epithelial layer to expose stroma. In another technique, thestromal surface is exposed by removing an epithelial layer to exposestroma. In some techniques, an additional step of replacing theepithelial layer to at least partially cover the implant 1400 isperformed.

After the flap 1408 is closed to cover at least a portion of the implant1400, the implant 1400 may be repositioned to some extent in someapplications. In one technique, pressure is applied to the implant 1400to move the implant into alignment with the reference point 1412. Thepressure may be applied to the anterior surface of the cornea 1404proximate an edge of the implant 1400 (e.g., directly above, above andoutside a projection of the outer periphery of the implant 1400, orabove and inside a projection of the outer periphery of the implant1400). This may cause the implant to move slightly away from the edgeproximate which pressure is applied. In another technique, pressure isapplied directly to the implant. The implant 1400 may be repositioned inthis manner if the reference point 1412 was marked on the flap 1408 orif the reference point 1412 was marked on the tissue bed. Preferably,pushing is accomplished by inserting a thin tool under the flap or intothe pocket and directly moving the inlay.

FIG. 53 shows that a patient may also be treated by a method thatpositions an implant 1500 in a cornea 1504, e.g., in a corneal pocket1508. Any suitable tool or technique may be used to create or form thecorneal pocket 1508. For example, a blade (e.g., a microkeratome), alaser, or an electrosurgical tool could be used to create or form apocket in the cornea 1504. A reference point 1512 is identified on thecornea 1504. The reference point may be identified by any suitabletechnique, such as those discussed herein. The reference point 1512 ismarked by any suitable technique, such as those discussed herein. Thecorneal pocket 1508 is created to expose an intracorneal surface 1516.The corneal pocket 1508 may be created at any suitable depth, forexample at a depth within a range of from about 50 microns to about 300microns from the anterior surface of the cornea 1504. The implant 1500is positioned on the intracorneal surface 1516. The marked referencepoint 1512 is helpful in positioning the implant 1500 on theintracorneal surface 1516. The marked reference point 1512 enables theimplant 1500 to be positioned with respect to the visual axis of theeye, as discussed above. In the illustrated embodiment, the implant 1500is positioned so that a centerline M_(CL) of the implant 1500 extendsthrough or adjacent to the marked reference point 1512.

FIG. 53A illustrates another technique wherein a reference 1512′ is aring or other two dimensional mark. In such case, the implant 1500 maybe placed so that an outer edge of the implant and the ring correspond,e.g., such that the ring and the implant 1500 share the same orsubstantially the same center. Preferably, the ring and the implant 1500are aligned so that the centerline of the implant M_(CL) is on the lineof sight of the eye, as discussed above. The ring is shown in solidlines because in the illustrated embodiment, it is formed on theanterior surface of the cornea 1504 above the pocket 1508.

After the implant 1500 is positioned in the pocket 1508, the implant1500 may be repositioned to some extent in some applications. In onetechnique, pressure is applied to the implant 1500 to move the implantinto alignment with the reference point 1512. The pressure may beapplied to the anterior surface of the cornea 1504 proximate an edge ofthe implant 1500 (e.g., directly above, above and outside a projectionof the outer periphery of the implant 1500, or above and inside aprojection of the outer periphery of the implant 1500). This may causethe implant 1500 to move slightly away from the edge at which pressureis applied. In another technique, pressure is applied directly to theimplant 1500.

VIII. Further Masks Configured to Reduce Visibile Diffraction Patternsand Provide Nutrient Transport

Perforating a corneal inlay to provide nutrient transport can have thedisadvantage that light also passes through the holes. Lighttransmission can reduce the opacity of the annulus to the point ofdegrading the optical performance of the inlay in some conditions. Indim light conditions for distance vision, increased light transmissionthrough the annulus can increase the overall optical performance byincreasing illumination of the retina. While this light may help withdistance vision in dim conditions, it may decrease the quality of nearvision. Therefore, it is desirable to limit the transmission of lightwhile enhancing transmission of nutrients.

The inventors recognized that while nutrient transport through thecornea is largely in the posterior-anterior direction, nutrients alsocan flow laterally around edges of an inlay. Lateral flow of nutrientscan be driven by a gradient of concentration, for example. Thus, even ifan impermeable barrier is positioned in a small portion of the cornea,the tissue above the barrier benefits from lateral diffusion, and is notas nutrient-depleted as it would be without lateral diffusion. Thecloser a region of corneal tissue is to an edge of a nutrient barrier,the less at risk this tissue is to nutrient depletion. Accordingly, aninlay need not have as many perforations at locations near edges as maybe at locations farther from edges. Conversely, depletion is at itsgreatest in the center of a nutrient barrier. Accordingly, there is anadvantage to increasing porosity near the center of a nutrient barrierto compensate for the relatively lower lateral flow of nutrients in thatcentral region. Thus, the inlay can be optimized to maintain the healthof the cornea.

It is possible to design a hole pattern which transmits less lightoverall, but provides better nutrient transport where it is needed mostby creating a gradient of porosity that increases toward a centralregion of a nutrient blocking structure of an inlay. For example, anarrangement can be provided in which a gradient of porosity is least atthe edges and greatest in a central section of an annulus of an inlay.Increasing porosity can be accomplished in a number of ways. Forexample, FIG. 55 illustrates an annular corneal inlay 3100 with holes3102 providing porosity, the holes 3102 being generally randomlyarranged, the holes 3102 having substantially the same diameter acrossthe annulus. This pattern could be modified to have a greater number ofholes toward a central region of the annulus in some embodiments. Whilethe number of holes toward the central region can be increased, thegenerally random positioning of the holes is maintained in someembodiments to prevent the holes from producing visible diffractionpatterns or other optical artifacts.

As described above in Section V above, other embodiments may be providedthat vary at least one aspect of a plurality of holes to reduce thetendency of the holes to produce visible diffraction patterns orpatterns that otherwise reduce the vision improvement that may beprovided by a mask with an aperture or opening. For example, in oneembodiment, the hole size, shape, and orientation of at least asubstantial number of the holes may be varied randomly or may beotherwise non-uniform. The mask may also be characterized in that atleast one of the hole size, shape, orientation, and spacing of aplurality of holes is varied to reduce the tendency of the holes toproduce visible diffraction patterns. In certain embodiments, thetendency of the holes to produce visible diffraction patterns is reducedby having a plurality of the holes having a first hole size, shape, orspacing and at least another plurality of the holes with a second holesize, shape, or spacing different from the first hole size, shape, orspacing. In other embodiments, the mask is characterized in that atleast one of the hole size, shape, orientation, and spacing of asubstantial number of the plurality of holes is different than at leastone of the hole size, shape, orientation, and spacing of at leastanother substantial number of the plurality of holes to reduce thetendency of the holes to produce visible diffraction patterns. Infurther embodiments, the holes are positioned at irregular locations.For example, the holes are positioned at irregular locations to minimizethe generation of visible artifacts due to the transmission of lightthrough the holes.

FIG. 56 illustrates an annular corneal inlay with holes providingporosity for nutrient transport, the holes being generally randomlyarranged. The holes in the embodiment of FIG. 56 are not substantiallythe same hole diameter across the annulus. Rather, the holes havedifferent hole diameters in different regions of the mask. For example,as discussed in greater detail below, the holes have larger diameters ina central region of the inlay than near the inner and outercircumferences of the inlay to enhance porosity of the inlay toward thecentral region. Additional hole patterns and arrangements optimized fornutrient flow are discussed in U.S. Pat. No. 7,628,810, U.S. PatentPublication No. 2006-0113054, and U.S. Patent Publication No.2006-0265058, the entirety of each of which is hereby incorporated byreference.

The mask illustrated in FIG. 55 has an irregular hole pattern with holesthat are substantially the same size. In one embodiment, the holes havea diameter of about 10 microns. The embodiment of the mask illustratedin FIG. 56 has an irregular hole pattern. The mask includes an innerperipheral region neighboring (e.g., immediately adjacent to) the innerperiphery of the mask, an outer peripheral region neighboring (e.g.,immediately adjacent to) the outer periphery of the mask, and aplurality of annular bands between the inner periphery region and theouter periphery region. The bands can be modified such that there is agenerally increasing porosity from at least one of the inner or outerperiphery regions toward a central portion of the annulus. For example,in one arrangement, a fixed number of holes is located in each band,with the size of the holes being larger in bands closer to the center ofthe annulus than in bands that are farther from the center of theannulus.

FIG. 57 illustrates an embodiment of a mask 3000 that includes a body3004 with an aperture or opening 3002. The body 3004 includes a holeregion 3010 between an outer periphery 3012 and an inner periphery 3014of the body 3004. The hole region 3010 includes a nutrient transportstructure 3030. Only a portion of the nutrient transport structure 3030is shown for simplicity. The hole region 3010 can include two moresub-regions, and each sub-region includes a plurality of holes. Eachsub-region can have at least one property that is different from atleast one property of another sub-region. For example, properties of asub-region can include average or mean hole size (radius, diameter,area, perimeter, etc.), number of holes per unit area (e.g., holedensity), area of holes per unit area (e.g., percentage of sub-regionarea that includes holes), shape of the holes, spacing between holes,percentage of light transmission, percentage of nutrient depletion,nutrient transport rate (e.g., nutrient transport rate per unit area),or porosity. FIG. 57 illustrates one embodiment with three sub-regionsincluding an inner region 3020, an outer region 3022, and a centralregion 3024 between the inner region 3020 and the outer region 3022. Theinner region 3020 is located between the inner periphery 3014 and aselected first circumference 3026, the outer region 3022 is locatedbetween the outer periphery 2012 and a selected second circumference3028, and the central region is located between the selected firstcircumference 3026 and the selected second circumference 3028. Each ofthe sub-regions can have an area that is the same or different from anarea of another sub-regions. For example, each sub-region may or may notbe equally spaced radially from the center of the aperture. In certainembodiments, each sub-region is an annular band.

As discussed previously, the body 3004 may also include an innerperipheral region 3008 and/or an outer peripheral region 3006 that aresubstantially devoid of holes. The inner peripheral region 3008 canextend between the inner periphery 3014 and a selected innercircumference 3018, and the outer peripheral region 3006 can extendbetween the outer periphery 3012 and a selected outer circumference3016.

Nutrient depletion can be greatest near the center of the annulus (e.g.,about midway between the outer periphery 3012 and the inner periphery3014. Therefore, more hole area or porosity that allows nutrienttransportion through the mask 3000 near the center of the annulus candecrease nutrient depletion caused by the mask 3000. In certainembodiments, the central region 3024 has a greater ability to transportnutrients than the inner region 3020 and/or the outer region 3022. Forexample, the central region 3024 has a central area and the plurality ofholes in the central region 3024 may comprise a first percentage of thecentral area. Similarly, the inner region 3020 has an inner area and theplurality of holes in the inner region 3020 may comprise a secondpercentage of the inner area, and the outer region 3022 has an outerarea and the plurality of holes in the outer region 3022 may comprise athird percentage of the outer area. The first percentage can be greaterthan the second percentage and/or the third percentage. In anotherexample, the central region 3024 may include a first porosity, the innerregion 3020 may include a second porosity, the outer region 3024 mayinclude a third porosity, and the first porosity is greater than thesecond porosity and/or the third porosity. In other words, the centralregion 3024, the inner region 3020, and the outer region 3022 caninclude a nutrient transport property that improves nutrient transportthrough the mask 3000. The central region 3024 can include a firstnutrient transport property value, the inner region 3020 can include asecond nutrient transport property value, the outer region 3022 caninclude a third nutrient transport property value, and the firstnutrient transport property value can be greater than the second and/orthird nutrient transport property value. The nutrient transport propertycan be, for example, porosity, hole percentage, hole size, number ofholes per unit area, or nutrient transport rate.

The position of the sub-regions can have a variety of configurations. Incertain embodiments, the central region is located at between about 10to about 90 percent of the annular width of the mask from the innerperiphery. In additional embodiments, the central region is located atbetween about 20 to about 60 percent, between about 30 and about 50percent, or between about 30 and 40 percent of the annular width of themask from the inner periphery.

The hole region 3010 may also include more than three regions (e.g.,inner, outer, and central regions) that are described above. The holeregion 3010 can include any number of regions from two to infinity. Forexample, the hole region 3010 can gradually change one or propertiesradially across the mask body 3004 and may not change in a step fashion.In one embodiment, the porosity increases and then decreases radiallyfrom the inner periphery to the outer periphery. For example, theporosity may be substantially zero at or near the inner periphery andgradually increase to a maximum porosity and then gradually decrease tobe substantially zero at or near the outer periphery.

In one arrangement, as illustrated in FIG. 56, ten annular bands aredisposed between the inner periphery region and the outer peripheryregion. The first band of the ten annular bands neighbors (e.g., isimmediately adjacent to) the inner periphery region, the second bandneighbors the first band, and so forth. The tenth band neighbors theouter periphery region. Each band includes 840 holes in one embodiment.The inner periphery region and outer periphery region can take anysuitable form, but preferably include no holes. The radial width of thesize of inner periphery region and outer periphery region can be anysuitable width, for example optimized to maintain the mechanicalintegrity of the inlay or to provide for handling by a user. In oneembodiment, the inner periphery region and outer periphery region are 50about microns wide. In some embodiments, only one of the inner peripheryregion and outer periphery region is provided. In other words, one ofthe bands with holes can be located at the inner periphery or the outerperiphery.

One embodiment is further described in Table I. Each of the bands has aband width, a percentage of light transmission through the band, and ahole diameter for the holes in the band, as illustrated in Table I. Inthe embodiment of Table I, the bands are configured to be of equal area,and thus have progressively smaller widths farther from the innerperiphery of the inlay. However, annular bands can be provided withdifferent areas between the inner periphery and the outer periphery insome embodiments.

TABLE I Properties of one embodiment of the inlay of FIG. 56. HoleDiameter Band Width Band No. (microns) % Transmission (microns) 1 5.452.3 146 2 7.45 4.3 127 3 9.45 6.9 114 4 11.45 10.2 105 5 10.45 8.5 97 69.45 6.9 91 7 8.45 5.6 86 8 7.45 4.3 81 9 6.45 3.2 78 10 5.45 2.3 74

In some embodiments, the central portion of the light blocking portionof the inlay (e.g., a midline of the annulus) is farthest from a sourceof lateral nutrient flow. In such an embodiment, it may be desirable tolocate the portion (e.g., the band) of greatest porosity at or aroundthe central portion. In other embodiments, the peak porosity can belocated between the mid-line of the annulus and the inner periphery. Insome applications of a small aperture inlay, lateral flow emanating fromthe aperture at the inner periphery of the inlay and propagating outwardthrough corneal tissue anterior and/or posterior of the annulus isexpected to be less than lateral flow emanating from tissue radiallyoutward of the outer periphery and propagating inward through cornealtissue anterior and/or posterior of the annulus. In one embodiment, thelocation of peak porosity is at about 40 percent or less of the annularwidth of the inlay from the inner periphery. Such an arrangementprovides a higher percentage of total nutrient flow to tissue anteriorand/or posterior of an inner portion of the annulus from the nutrientflow structure than is provided to similar tissue adjacent to an outerportion of the annulus.

In the embodiment of the inlay of FIG. 56 described by Table I, themodeled average light transmission is about 5%. In the embodiment of theinlay of FIG. 55, the modeled average light transmission is about 6.75%.The inlays of FIGS. 55 and 56 have an inner radius of 0.8 mm (e.g., anaperture with a diameter of 1.6 mm), and an outer radius of 1.9 mm(e.g., radial distance from the center of the aperture to the outerperiphery of the inlay.

FIG. 58 illustrates a comparison of modeled glucose depletion in acornea in which the inlays of FIGS. 55 and 56 have been implanted as afunction of radial distances from the center of the inlay or aperture.FIG. 58 was obtained from a finite-element model of glucose transport inthe human cornea. The inlays of FIGS. 55 and 56 extend from the innerperiphery at a radial distance of 0.8 mm to the outer periphery at aradial distance of 1.9 mm. The radial distance from the center of theaperture plotted in FIG. 58 starts at 0 mm (e.g., center of theaperture) and goes to greater than 1.9 mm (e.g., greater than the outerperiphery of the inlay). From FIG. 58, it is clear that increasing theporosity, in this case, by increasing the size of holes near the annulusmidline, can reduce glucose depletion. In particular, FIG. 58 shows thatthe embodiment of FIG. 56 reduces depletion of glucose while at the sametime decreasing the overall porosity or hole density from 6.75% to 5%.The reduced light transmission of the mask of FIG. 56 compared to themask of FIG. 55 improves the visual acuity produced by the mask.Therefore, advantageously, the mask of FIG. 56 has both improvednutrient transport and visual acuity compared to the mask of FIG. 55.

Various embodiments have been described above. Although the inventionhas been described with reference to these specific embodiments, thedescriptions are intended to be illustrative and are not intended to belimiting. Various modifications and applications may occur to thoseskilled in the art without departing from the true spirit and scope ofthe invention as defined in the appended claims.

1. A corneal inlay comprising: an anterior surface configured to resideadjacent a first corneal layer; a posterior surface configured to resideadjacent a second corneal layer; an opening configured to transmit lighttherethrough; an outer zone adapted to substantially preventtransmission of light therethrough, the outer zone having nutrienttransport structures disposed therein, the outer zone being configuredto provide enhanced nutrient flow at locations spaced away from an outerperiphery of the outer zone compared with locations adjacent to theouter periphery of the outer zone.
 2. The corneal inlay of claim 1,wherein the outer zone comprises a first region and a second region atleast partially disposed between the first region and the opening; andfurther wherein each of the first and second regions comprises nutrienttransport structures disposed therein and one of the first and secondregions is configured to have enhanced nutrient transport compared withthe other of the first and second regions.
 3. The corneal inlay of claim2, further comprising a third region disposed between the region withenhanced nutrient transport and an outer or inner periphery of thecorneal inlay.
 4. The corneal inlay of claim 3, wherein the region withenhanced nutrient transport is configured to have greater nutrienttransport than the third region.
 5. The corneal inlay of claim 4,further comprising a first annular band disposed adjacent the openingand a second annular band disposed adjacent the outer periphery.
 6. Thecorneal inlay of claim 1, further comprising one or more annular bandsdisposed adjacent the opening, adjacent an outer periphery of thecorneal inlay, or both adjacent the opening and the outer periphery ofthe corneal inlay.
 7. The corneal inlay of claim 1, wherein thelocations spaced away from the outer periphery have higher porosity thanlocations adjacent to the outer periphery.
 8. A mask configured to beimplanted in a cornea of a patient to increase the depth of focus of thepatient, the mask comprising: an anterior surface configured to resideadjacent a first corneal layer; a posterior surface configured to resideadjacent a second corneal layer; an aperture configured to transmitlight therethrough; a substantially opaque portion extending at leastpartially between the aperture and an outer periphery of the mask, theopaque portion comprising an inner region, an outer region, and acentral region disposed between the inner and outer regions; a pluralityof holes disposed in the inner, outer and central regions and extendingbetween the anterior surface and the posterior surface; and wherein thecentral region comprises a first porosity, the inner region comprises asecond porosity, the outer region comprises a third porosity, and thefirst porosity is greater than the second porosity or the thirdporosity.
 9. The mask of claim 8, wherein the holes in central regionhave an average hole size that is greater than an average hole size ofthe holes in the inner region and an average hole size of the holes inthe outer region.
 10. The mask of claim 9, wherein the inner, outer, andcentral regions comprise about the same number of holes per unit area.11. The mask of claim 8, wherein first porosity is greater than thesecond porosity and the third porosity.
 12. The mask of claim 8, whereinthe central region is located at less than about 40 percent of theannular width of the mask from the inner periphery.
 13. The mask ofclaim 8, wherein a maximum porosity is located at about 40 percent orless of the annular width of the mask from the inner periphery.
 14. Themask of claim 8, wherein the holes are positioned at irregular locationsto minimize the generation of visible artifacts due to the transmissionof light through the holes.
 15. The mask of claim 8, wherein thetendency of the holes to produce visible diffraction patterns is reducedby having a plurality of the holes having a first hole size, shape, orspacing and at least another plurality of the holes with a second holesize, shape, or spacing different from the first hole size, shape, orspacing.
 16. The mask of claim 8, further comprising an inner peripheralregion disposed between the inner region and an inner periphery of themask, the inner peripheral region substantially devoid of holes.
 17. Themask of claim 8, further comprising an outer peripheral region disposedbetween the outer region and an outer periphery of the mask, the outerperipheral region substantially devoid of holes.
 18. The mask of claim17, further comprising an inner peripheral region disposed between theinner region and an inner periphery of the mask, the inner peripheralregion substantially devoid of holes.
 19. A mask configured to beimplanted in a cornea of a patient to increase the depth of focus of thepatient, the mask comprising: an anterior surface configured to resideadjacent a first corneal layer; a posterior surface configured to resideadjacent a second corneal layer; an aperture configured to transmitlight therethrough; a substantially opaque portion extending at leastpartially between the aperture and an outer periphery of the mask, theopaque portion comprising an inner region, an outer region, and acentral region disposed between the inner and outer regions; wherein thecentral region comprises a first nutrient transport rate between theposterior and anterior surfaces, the inner region comprises a secondnutrient transport rate between the posterior and anterior surfaces, theouter region comprises a third nutrient transport rate between theposterior and anterior surfaces, and the first nutrient transport rateis greater than the second or third nutrient transport rates.
 20. Amethod for improving the vision of a patient, the method comprising:providing a mask comprising an anterior surface configured to resideadjacent a first corneal layer, a posterior surface configured to resideadjacent a second corneal layer, an aperture configured to transmitalong an optic axis substantially all incident light, a substantiallyopaque portion extending at least partially between the aperture and anouter periphery of the mask, the opaque portion comprising an innerregion, an outer region, and a central region disposed between the innerand outer regions, a plurality of holes extending between the anteriorsurface and the posterior surface, and wherein the holes are positionedat locations in the inner, outer and central regions, and the centralregion comprises a first porosity, the inner region comprises a secondporosity, the outer region comprises a third porosity, and the firstporosity is greater than the second porosity or the third porosity; andinserting the mask into a cornea.